Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications
Abstract
:Simple Summary
Abstract
1. Introduction
2. Extracellular Vesicles
2.1. Exosome Biogenesis
2.2. EV Release from the Cell Surface
2.3. Exomeres
2.4. EVs in Cell Communication
2.5. Regulation of EV Release in Cancer
3. EV-Mediated Function in Cancer
3.1. Sustaining Proliferative Signaling
3.2. Evading Growth Suppressors
3.3. Resisting Cell Death
3.4. Enabling Replicative Immortality
3.5. Inducing Angiogenesis
3.6. Invasion and Metastasis
3.7. Genome Instability and Mutation
3.8. Tumor-Promoting Inflammation
3.9. Deregulating Cellular Energetics
3.10. Avoiding Immune Destruction
3.11. EVs and Thrombosis
3.12. EVs and Cell Competition
4. EVs in Cancer Drug Resistance
4.1. EV-Mediated Drug Transport
4.2. EVs Transport Drug Efflux Pumps
4.3. EVs Transfer Pro-Survival Cargos
4.4. EVs Mediate Drug Resistance via the Transfer of microRNAs
4.5. EV Interference in Immunotherapies
5. EVs in Organ Tropism, Drug Delivery, Imaging and Theranosis
5.1. EV Organ Tropism
5.2. EVs as Drug Delivery Vehicles
5.3. EV Imaging for Cancer Diagnosis
5.4. EVs for Theranostic Applications
6. EVs and Cancer Patient Survival
7. Concluding Remarks
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Chargaff, E.; West, R. The biological significance of the thromboplastic protein of blood. J. Biol. Chem. 1946, 166, 189–197. [Google Scholar] [CrossRef]
- Wolf, P. The Nature and Significance of Platelet Products in Human Plasma. Br. J. Haematol. 1967, 13, 269–288. [Google Scholar] [CrossRef] [PubMed]
- Yáñez-Mó, M.; Siljander, P.R.-M.; Andreu, Z.; Zavec, A.B.; Borràs, F.E.; Buzas, E.I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; et al. Biological Properties of Extracellular Vesicles and their Physiological Functions. J. Extracell. Vesicles 2015, 4, 27066. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aheget, H.; Mazini, L.; Martin, F.; Belqat, B.; Marchal, J.A.; Benabdellah, K. Exosomes: Their Role in Pathogenesis, Diagnosis and Treatment of Diseases. Cancers 2020, 13, 84. [Google Scholar] [CrossRef]
- Shao, H.; Im, H.; Castro, C.M.; Breakefield, X.; Weissleder, R.; Lee, H. New Technologies for Analysis of Extracellular Vesicles. Chem. Rev. 2018, 118, 1917–1950. [Google Scholar] [CrossRef]
- Van Niel, G.; D’Angelo, G.; Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 2018, 19, 213–228. [Google Scholar] [CrossRef] [PubMed]
- Caby, M.-P.; Lankar, D.; Vincendeau-Scherrer, C.; Raposo, G.; Bonnerot, C. Exosomal-like vesicles are present in human blood plasma. Int. Immunol. 2005, 17, 879–887. [Google Scholar] [CrossRef] [Green Version]
- Gonzales, P.A.; Zhou, H.; Pisitkun, T.; Wang, N.S.; Star, R.A.; Knepper, M.A.; Yuen, P.S.T. Isolation and Purification of Exosomes in Urine. Methods Mol. Biol. 2010, 641, 89–99. [Google Scholar] [CrossRef]
- Gomez, C.D.L.T.; Goreham, R.V.; Serra, J.J.B.; Nann, T.; Kussmann, M. “Exosomics”—A Review of Biophysics, Biology and Biochemistry of Exosomes with a Focus on Human Breast Milk. Front. Genet. 2018, 9, 92. [Google Scholar] [CrossRef] [Green Version]
- Ding, X.-Q.; Wang, Z.-Y.; Xia, D.; Wang, R.-X.; Pan, X.-R.; Tong, J.-H. Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer. Front. Oncol. 2020, 10, 1113. [Google Scholar] [CrossRef]
- Mir, B.; Goettsch, C. Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo. Cells 2020, 9, 1601. [Google Scholar] [CrossRef] [PubMed]
- Roy, S.; Lin, H.-Y.; Chou, C.-Y.; Huang, C.-H.; Small, J.; Sadik, N.; Ayinon, C.M.; Lansbury, E.; Cruz, L.; Yekula, A.; et al. Navigating the Landscape of Tumor Extracellular Vesicle Heterogeneity. Int. J. Mol. Sci. 2019, 20, 1349. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xavier, C.P.R.; Caires, H.R.; Barbosa, M.A.G.; Bergantim, R.; Guimarães, J.E.; Vasconcelos, M.H. The Role of Extracellular Vesicles in the Hallmarks of Cancer and Drug Resistance. Cells 2020, 9, 1141. [Google Scholar] [CrossRef] [PubMed]
- Campos, A.; Salomon, C.; Bustos, R.; Díaz, J.; Martínez, S.; Silva, V.; Reyes, C.; Diaz-Valdivia, N.; Varas-Godoy, M.; Lobos-Gonzalez, L.; et al. Caveolin-1-containing extracellular vesicles transport adhesion proteins and promote malignancy in breast cancer cell lines. Nanomedicine 2018, 13, 2597–2609. [Google Scholar] [CrossRef] [Green Version]
- Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750. [Google Scholar] [CrossRef] [Green Version]
- Hanahan, D.; Weinberg, R.A. Hallmarks of Cancer: The Next Generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [Green Version]
- Meng, X.; Pan, J.; Sun, S.; Gong, Z. Circulating exosomes and their cargos in blood as novel biomarkers for cancer. Transl. Cancer Res. 2018, 7, S226–S242. [Google Scholar] [CrossRef]
- Huang, T.; Deng, C.-X. Current Progresses of Exosomes as Cancer Diagnostic and Prognostic Biomarkers. Int. J. Biol. Sci. 2019, 15, 1–11. [Google Scholar] [CrossRef]
- Armstrong, D.; Wildman, D.E. Extracellular Vesicles and the Promise of Continuous Liquid Biopsies. J. Pathol. Transl. Med. 2018, 52, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Zhou, B.; Xu, K.; Zheng, X.; Chen, T.; Wang, J.; Song, Y.; Shao, Y.; Zheng, S. Application of exosomes as liquid biopsy in clinical diagnosis. Signal. Transduct. Target. Ther. 2020, 5, 1–14. [Google Scholar] [CrossRef]
- Surman, M.; Drożdż, A.; Stępień, E.; Przybyło, M. Extracellular Vesicles as Drug Delivery Systems-Methods of Production and Potential Therapeutic Applications. Curr. Pharm. Des. 2019, 25, 132–154. [Google Scholar] [CrossRef] [PubMed]
- Hernandez-Oller, L.; Seras-Franzoso, J.; Andrade, F.; Rafael, D.; Abasolo, I.; Gener, P.; Schwartz, S., Jr. Extracellular Vesicles as Drug Delivery Systems in Cancer. Pharmaceutics 2020, 12, 1146. [Google Scholar] [CrossRef]
- Lötvall, J.; Hill, A.F.; Hochberg, F.; Buzás, E.I.; Di Vizio, D.; Gardiner, C.; Gho, Y.S.; Kurochkin, I.V.; Mathivanan, S.; Quesenberry, P.; et al. Minimal Experimental Requirements for Definition of Extracellular Vesicles and their Functions: A Position Statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles 2014, 3, 26913. [Google Scholar] [CrossRef]
- Abels, E.R.; Breakefield, X.O. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell. Mol. Neurobiol. 2016, 36, 301–312. [Google Scholar] [CrossRef] [PubMed]
- Skryabin, G.O.; Komelkov, A.V.; Savelyeva, E.E.; Tchevkina, E.M. Lipid Rafts in Exosome Biogenesis. Biochemistry 2020, 85, 177–191. [Google Scholar] [CrossRef] [PubMed]
- Trajkovic, K.; Hsu, C.; Chiantia, S.; Rajendran, L.; Wenzel, D.; Wieland, F.; Schwille, P.; Brugger, B.; Simons, M. Ceramide Triggers Budding of Exosome Vesicles into Multivesicular Endosomes. Science 2008, 319, 1244–1247. [Google Scholar] [CrossRef] [PubMed]
- Catalano, M.; O’Driscoll, L. Inhibiting extracellular vesicles formation and release: A review of EV inhibitors. J. Extracell. Vesicles 2020, 9, 1703244. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Savina, A.; Vidal, M.; Colombo, M.I. The exosome pathway in K562 cells is regulated by Rab11. J. Cell Sci. 2002, 115, 2505–2515. [Google Scholar] [CrossRef] [PubMed]
- Hsu, C.; Morohashi, Y.; Yoshimura, S.-I.; Hoyos, N.M.; Jung, S.; Lauterbach, M.A.; Bakhti, M.; Grønborg, M.; Möbius, W.; Rhee, J.; et al. Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C. J. Cell Biol. 2010, 189, 223–232. [Google Scholar] [CrossRef]
- Ostrowski, M.; Carmo, N.; Krumeich, S.; Fanget, I.; Raposo, G.; Savina, A.; Moita, C.F.; Schauer, K.; Hume, A.; Freitas, R.P.; et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 2009, 12, 19–30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Akers, J.C.; Gonda, D.; Kim, R.; Carter, B.S.; Chen, C.C. Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neuro Oncol. 2013, 113, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Petrovčíková, E.; Vičíková, K.; Leksa, V. Extracellular vesicles–biogenesis, composition, function, uptake and therapeutic applications. Biologia 2018, 73, 437–448. [Google Scholar] [CrossRef]
- Muralidharan-Chari, V.; Clancy, J.; Plou, C.; Romao, M.; Chavrier, P.; Raposo, G.; D’Souza-Schorey, C. ARF6-Regulated Shedding of Tumor Cell-Derived Plasma Membrane Microvesicles. Curr. Biol. 2009, 19, 1875–1885. [Google Scholar] [CrossRef] [Green Version]
- Tan, C.F.; Teo, H.S.; Park, J.E.; Dutta, B.; Tse, S.W.; Leow, M.K.-S.; Wahli, W.; Sze, S.K. Exploring Extracellular Vesicles Biogenesis in Hypothalamic Cells through a Heavy Isotope Pulse/Trace Proteomic Approach. Cells 2020, 9, 1320. [Google Scholar] [CrossRef]
- Wang, T.; Gilkes, D.M.; Takano, N.; Xiang, L.; Luo, W.; Bishop, C.J.; Chaturvedi, P.; Green, J.J.; Semenza, G.L. Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis. Proc. Natl. Acad. Sci. USA 2014, 111, E3234–E3242. [Google Scholar] [CrossRef] [Green Version]
- Li, B.; Antonyak, M.A.; Zhang, J.; Cerione, R.A. RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 2012, 31, 4740–4749. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schlienger, S.; Campbell, S.; Claing, A. ARF1 regulates the Rho/MLC pathway to control EGF-dependent breast cancer cell invasion. Mol. Biol. Cell 2014, 25, 17–29. [Google Scholar] [CrossRef] [PubMed]
- Willms, E.; Cabañas, C.; Mäger, I.; Wood, M.J.A.; Vader, P. Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression. Front. Immunol. 2018, 9, 738. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, H.; Freitas, D.; Kim, H.S.; Fabijanic, K.; Li, Z.; Chen, H.; Mark, M.T.; Molina, H.; Benito-Martin, A.; Bojmar, L.; et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat. Cell Biol. 2018, 20, 332–343. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Higginbotham, J.N.; Jeppesen, D.; Yang, Y.-P.; Li, W.; McKinley, E.T.; Graves-Deal, R.; Ping, J.; Britain, C.M.; Dorsett, K.A.; et al. Transfer of Functional Cargo in Exomeres. Cell Rep. 2019, 27, 940–954.e6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zijlstra, A.; Di Vizio, D. Size matters in nanoscale communication. Nat. Cell Biol. 2018, 20, 228–230. [Google Scholar] [CrossRef] [PubMed]
- Anand, S.; Samuel, M.; Mathivanan, S. Exomeres: A New Member of Extracellular Vesicles Family. In Prokaryotic Cytoskeletons; Springer Science and Business Media LLC: Berlin, Germany, 2021; Volume 97, pp. 89–97. [Google Scholar]
- Zhang, Q.; Jeppesen, D.K.; Higginbotham, J.N.; Franklin, J.L.; Crowe, J.E.; Coffey, R.J. Angiotensin-converting Enzyme 2–containing Small Extracellular Vesicles and Exomeres Bind the Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein. Gastroenterology 2021, 160, 958–961.e3. [Google Scholar] [CrossRef]
- Monteil, V.; Kwon, H.; Prado, P.; Hagelkrüys, A.; Wimmer, R.A.; Stahl, M.; Leopoldi, A.; Garreta, E.; Hurtado Del Pozo, C.; Prosper, F.; et al. Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2. Cell 2020, 181, 905–913.e7. [Google Scholar] [CrossRef]
- McKelvey, K.J.; Powell, K.L.; Ashton, A.W.; Morris, J.M.; McCracken, S.A. Exosomes: Mechanisms of Uptake. J. Circ. Biomark. 2015, 4, 7. [Google Scholar] [CrossRef] [Green Version]
- Jadli, A.S.; Ballasy, N.; Edalat, P.; Patel, V.B. Inside(sight) of tiny communicator: Exosome biogenesis, secretion, and uptake. Mol. Cell. Biochem. 2020, 467, 77–94. [Google Scholar] [CrossRef] [PubMed]
- Simons, M.; Raposo, G. Exosomes–vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 2009, 21, 575–581. [Google Scholar] [CrossRef]
- Huang, M.-B.; Xia, M.; Gao, Z.; Zhou, H.; Liu, M.; Huang, S.; Zhen, R.; Wu, J.Y.; Roth, W.W.; Bond, V.C.; et al. Characterization of Exosomes in Plasma of Patients with Breast, Ovarian, Prostate, Hepatic, Gastric, Colon, and Pancreatic Cancers. J. Cancer Ther. 2019, 10, 382–399. [Google Scholar] [CrossRef] [Green Version]
- Kim, H.K.; Song, K.S.; Park, Y.S.; Kang, Y.H.; Lee, Y.J.; Lee, K.R.; Ryu, K.W.; Bae, J.M.; Kim, S. Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: Possible role of a metastasis predictor. Eur. J. Cancer 2003, 39, 184–191. [Google Scholar] [CrossRef]
- Baran, J.; Baj-Krzyworzeka, M.; Weglarczyk, K.; Szatanek, R.; Zembala, M.; Barbasz, J.; Czupryna, A.; Szczepanik, A.; Zembala, M. Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol. Immunother. 2010, 59, 841–850. [Google Scholar] [CrossRef]
- Caivano, A.; Laurenzana, I.; De Luca, L.; La Rocca, F.; Simeon, V.; Trino, S.; D’Auria, F.; Traficante, A.; Maietti, M.; Izzo, T.; et al. High serum levels of extracellular vesicles expressing malignancy-related markers are released in patients with various types of hematological neoplastic disorders. Tumor Biol. 2015, 36, 9739–9752. [Google Scholar] [CrossRef] [PubMed]
- Giusti, I.; D’Ascenzo, S.; Dolo, V. Microvesicles as Potential Ovarian Cancer Biomarkers. BioMed Res. Int. 2013, 2013, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Messenger, S.W.; Woo, S.S.; Sun, Z.; Martin, T.F.J. A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4. J. Cell Biol. 2018, 217, 2877–2890. [Google Scholar] [CrossRef]
- Augimeri, G.; La Camera, G.; Gelsomino, L.; Giordano, C.; Panza, S.; Sisci, D.; Morelli, C.; Győrffy, B.; Bonofiglio, D.; Andò, S.; et al. Evidence for Enhanced Exosome Production in Aromatase Inhibitor-Resistant Breast Cancer Cells. Int. J. Mol. Sci. 2020, 21, 5841. [Google Scholar] [CrossRef]
- McAndrews, K.M.; Kalluri, R. Mechanisms associated with biogenesis of exosomes in cancer. Mol. Cancer 2019, 18, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Hanahan, D.; Weinberg, R.A. The Hallmarks of Cancer. Cell 2000, 100, 57–70. [Google Scholar] [CrossRef] [Green Version]
- Gutkin, A.; Uziel, O.; Beery, E.; Nordenberg, J.; Pinchasi, M.; Goldvaser, H.; Henick, S.; Goldberg, M.; Lahav, M. Tumor cells derived exosomes contain hTERT mRNA and transform nonmalignant fibroblasts into telomerase positive cells. Oncotarget 2016, 7, 59173–59188. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Skog, J.; Würdinger, T.; Van Rijn, S.; Meijer, D.H.; Gainche, L.; Curry, W.T., Jr.; Carter, B.S.; Krichevsky, A.M.; Breakefield, X.O. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 2008, 10, 1470–1476. [Google Scholar] [CrossRef] [PubMed]
- Meckes, D.G.; Shair, K.H.Y.; Marquitz, A.R.; Kung, C.-P.; Edwards, R.H.; Raab-Traub, N. Human tumor virus utilizes exosomes for intercellular communication. Proc. Natl. Acad. Sci. USA 2010, 107, 20370–20375. [Google Scholar] [CrossRef] [Green Version]
- Ohshima, K.; Inoue, K.; Fujiwara, A.; Hatakeyama, K.; Kanto, K.; Watanabe, Y.; Muramatsu, K.; Fukuda, Y.; Ogura, S.-I.; Yamaguchi, K.; et al. Let-7 MicroRNA Family Is Selectively Secreted into the Extracellular Environment via Exosomes in a Metastatic Gastric Cancer Cell Line. PLoS ONE 2010, 5, e13247. [Google Scholar] [CrossRef] [Green Version]
- Beckler, M.D.; Higginbotham, J.N.; Franklin, J.L.; Ham, A.-J.; Halvey, P.J.; Imasuen, I.E.; Whitwell, C.; Li, M.; Liebler, D.; Coffey, R.J. Proteomic Analysis of Exosomes from Mutant KRAS Colon Cancer Cells Identifies Intercellular Transfer of Mutant KRAS. Mol. Cell. Proteom. 2013, 12, 343–355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Choi, D.-Y.; You, S.; Jung, J.H.; Lee, J.C.; Rho, J.K.; Lee, K.Y.; Freeman, M.R.; Kim, K.P.; Kim, J. Extracellular vesicles shed from gefitinib-resistant nonsmall cell lung cancer regulate the tumor microenvironment. Proteomics 2014, 14, 1845–1856. [Google Scholar] [CrossRef] [PubMed]
- Carvalho, A.S.; Baeta, H.; Silva, B.C.; Moraes, M.C.S.; Bodo, C.; Beck, H.C.; Rodriguez, M.S.; Saraswat, M.; Pandey, A.; Matthiesen, R. Extra-cellular vesicles carry proteome of cancer hallmarks. Front. Biosci. Landmark Ed. 2020, 25, 398–436. [Google Scholar]
- Yoshii, S.; Hayashi, Y.; Iijima, H.; Inoue, T.; Kimura, K.; Sakatani, A.; Nagai, K.; Fujinaga, T.; Hiyama, S.; Kodama, T.; et al. Exosomal microRNAs derived from colon cancer cells promote tumor progression by suppressing fibroblast TP53 expression. Cancer Sci. 2019, 110, 2396–2407. [Google Scholar] [CrossRef] [Green Version]
- Khoo, X.-H.; Paterson, I.C.; Goh, B.-H.; Lee, W.-L. Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles. Cancers 2019, 11, 1166. [Google Scholar] [CrossRef] [Green Version]
- Wheatley, S.P.; Altieri, D.C. Survivin at a glance. J. Cell Sci. 2019, 132, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Radeghieri, A.; Savio, G.; Zendrini, A.; Di Noto, G.; Salvi, A.; Bergese, P.; Piovani, G. Cultured human amniocytes express hTERT, which is distributed between nucleus and cytoplasm and is secreted in extracellular vesicles. Biochem. Biophys. Res. Commun. 2017, 483, 706–711. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taraboletti, G.; D’Ascenzoy, S.; Giusti, I.; Marchetti, D.; Borsotti, P.; Millimaggi, D.; Giavazzi, R.; Pavan, A.; Dolo, V. Bioavailability of VEGF in Tumor-Shed Vesicles Depends on Vesicle Burst Induced by Acidic pH. Neoplasia 2006, 8, 96–103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Al-Nedawi, K.; Meehan, B.; Kerbel, R.S.; Allison, A.C.; Rak, J. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc. Natl. Acad. Sci. USA 2009, 106, 3794–3799. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mineo, M.; Garfield, S.H.; Taverna, S.; Flugy, A.; De Leo, G.; Alessandro, R.; Kohn, E.C. Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion. Angiogenesis 2011, 15, 33–45. [Google Scholar] [CrossRef] [Green Version]
- Li, C.C.Y.; Eaton, S.A.; Young, P.E.; Lee, M.; Shuttleworth, R.; Humphreys, D.; Grau, G.; Combes, V.; Bebawy, M.; Gong, J.; et al. Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells. RNA Biol. 2013, 10, 1333–1344. [Google Scholar] [CrossRef] [Green Version]
- Ludwig, N.; Whiteside, T.L. Potential roles of tumor-derived exosomes in angiogenesis. Expert Opin. Ther. Targets 2018, 22, 409–417. [Google Scholar] [CrossRef]
- Hakulinen, J.; Sankkila, L.; Sugiyama, N.; Lehti, K.; Keski-Oja, J. Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes. J. Cell. Biochem. 2008, 105, 1211–1218. [Google Scholar] [CrossRef] [PubMed]
- Atay, S.; Banskota, S.; Crow, J.; Sethi, G.; Rink, L.; Godwin, A.K. Oncogenic KIT-containing exosomes increase gastrointestinal stromal tumor cell invasion. Proc. Natl. Acad. Sci. USA 2014, 111, 711–716. [Google Scholar] [CrossRef] [Green Version]
- Kobayashi, M.; Salomon, C.; Tapia, J.; Illanes, E.S.; Mitchell, M.D.; Rice, E.G. Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200. J. Transl. Med. 2014, 12, 4. [Google Scholar] [CrossRef] [Green Version]
- Alečković, M.; Kang, Y. Regulation of cancer metastasis by cell-free miRNAs. Biochim. Biophys. Acta BBA Bioenerg. 2015, 1855, 24–42. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hoshino, A.; Costa-Silva, B.; Shen, T.-L.; Rodrigues, G.; Hashimoto, A.; Mark, M.T.; Molina, H.; Kohsaka, S.; Di Giannatale, A.; Ceder, S.; et al. Tumour exosome integrins determine organotropic metastasis. Nature 2015, 527, 329–335. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, X.; Ding, X.; Nan, L.; Wang, Y.; Wang, J.; Yan, Z.; Zhang, W.; Sun, J.; Zhu, W.; Ni, B.; et al. Investigation of the roles of exosomes in colorectal cancer liver metastasis. Oncol. Rep. 2015, 33, 2445–2453. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, Q.; Wu, H.; Xiao, Y.; Liang, Z.; Liu, T. Upregulation of exosomal microRNA-21 in pancreatic stellate cells promotes pancreatic cancer cell migration and enhances Ras/ERK pathway activity. Int. J. Oncol. 2020, 56, 1025–1033. [Google Scholar] [CrossRef] [PubMed]
- He, J.; He, J.; Min, L.; He, Y.; Guan, H.; Wang, J.; Peng, X. Extracellular vesicles transmitted miR-31-5p promotes sorafenib resistance by targeting MLH1 in renal cell carcinoma. Int. J. Cancer 2020, 146, 1052–1063. [Google Scholar] [CrossRef] [PubMed]
- Fabbri, M.; Paone, A.; Calore, F.; Galli, R.; Gaudio, E.; Santhanam, R.; Lovat, F.; Fadda, P.; Mao, C.; Nuovo, G.J.; et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc. Natl. Acad. Sci. USA 2012, 109, E2110–E2116. [Google Scholar] [CrossRef] [Green Version]
- Haderk, F.; Schulz, R.; Iskar, M.; Cid, L.L.; Worst, T.; Willmund, K.V.; Schulz, A.; Warnken, U.; Seiler, J.; Benner, A.; et al. Tumor-derived exosomes modulate PD-L1 expression in monocytes. Sci. Immunol. 2017, 2, eaah5509. [Google Scholar] [CrossRef] [Green Version]
- Kim, D.-K.; Lee, J.; Kim, S.R.; Choi, D.-S.; Yoon, Y.J.; Kim, J.H.; Go, G.; Nhung, D.; Hong, K.; Jang, S.C.; et al. EVpedia: A community web portal for extracellular vesicles research. Bioinformatics 2014, 31, 933–939. [Google Scholar] [CrossRef]
- Zhang, J.; Lu, S.; Zhou, Y.; Meng, K.; Chen, Z.; Cui, Y.; Shi, Y.; Wang, T.; He, Q.Y. Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes. Proteomics 2017, 17, 1–36. [Google Scholar]
- Xia, Y.; Zhang, Q.; Zhen, Q.; Zhao, Y.; Liu, N.; Li, T.; Hao, Y.; Zhang, Y.; Luo, C.; Wu, X. Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway. Oncotarget 2017, 8, 37783–37795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, G.; Huang, A.C.; Zhang, W.; Zhang, G.; Wu, M.; Xu, W.; Yu, Z.; Yang, J.; Wang, B.; Sun, H.; et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018, 560, 382–386. [Google Scholar] [CrossRef] [PubMed]
- Xie, F.; Xu, M.; Lu, J.; Mao, L.; Wang, S. The role of exosomal PD-L1 in tumor progression and immunotherapy. Mol. Cancer 2019, 18, 146. [Google Scholar] [CrossRef] [Green Version]
- Koga, K.; Matsumoto, K.; Akiyoshi, T.; Kubo, M.; Yamanaka, N.; Tasaki, A.; Nakashima, H.; Nakamura, M.; Kuroki, S.; Tanaka, M.; et al. Purification, characterization and biological significance of tumor-derived exosomes. Anticancer Res. 2005, 25, 3703–3707. [Google Scholar]
- O’Brien, K.; Rani, S.; Corcoran, C.; Wallace, R.; Hughes, L.; Friel, A.; McDonnell, S.; Crown, J.; Radomski, M.W.; O’Driscoll, L. Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells. Eur. J. Cancer 2013, 49, 1845–1859. [Google Scholar] [CrossRef]
- Qu, J.-L.; Qu, X.-J.; Zhao, M.-F.; Teng, Y.-E.; Zhang, Y.; Hou, K.-Z.; Jiang, Y.-H.; Yang, X.-H.; Liu, Y.-P.; Qu, J.-L.; et al. Gastric cancer exosomes promote tumour cell proliferation through PI3K/Akt and MAPK/ERK activation. Dig. Liver Dis. 2009, 41, 875–880. [Google Scholar] [CrossRef]
- Yang, L.; Wu, X.-H.; Wang, D.; Luo, C.-L.; Chen, L.-X. Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro. Mol. Med. Rep. 2013, 8, 1272–1278. [Google Scholar] [CrossRef] [Green Version]
- Dai, G.; Yao, X.; Zhang, Y.; Gu, J.; Geng, Y.; Xue, F.; Zhang, J. Colorectal cancer cell–derived exosomes containing miR-10b regulate fibroblast cells via the PI3K/Akt pathway. Bull. Cancer 2018, 105, 336–349. [Google Scholar] [CrossRef]
- Lei, L.; Mou, Q. Exosomal taurine up-regulated 1 promotes angiogenesis and endothelial cell proliferation in cervical cancer. Cancer Biol. Ther. 2020, 21, 717–725. [Google Scholar] [CrossRef]
- Liu, S.; Sun, J.; Lan, Q. Glioblastoma microvesicles promote endothelial cell proliferation through Akt/beta-catenin pathway. Int. J. Clin. Exp. Pathol. 2014, 7, 4857–4866. [Google Scholar]
- Huang, J.; Ding, Z.; Luo, Q.; Xu, W. Cancer cell-derived exosomes promote cell proliferation and inhibit cell apoptosis of both normal lung fibroblasts and non-small cell lung cancer cell through delivering alpha-smooth muscle actin. Am. J. Transl. Res. 2019, 11, 1711–1723. [Google Scholar]
- Richards, K.E.; Zeleniak, A.E.; Fishel, M.; Wu, J.; Littlepage, L.E.; Hill, R. Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene 2017, 36, 1770–1778. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, Y.-Y.; Tao, Y.-W.; Gao, S.; Li, P.; Zheng, J.-M.; Zhang, S.-E.; Liang, J.; Zhang, Y. Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p. EBioMedicine 2018, 36, 209–220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pavlakis, E.; Neumann, M.; Stiewe, T. Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis. Int. J. Mol. Sci. 2020, 21, 9648. [Google Scholar] [CrossRef] [PubMed]
- Yu, X.; Harris, S.L.; Levine, A.J. The Regulation of Exosome Secretion: A Novel Function of the p53 Protein. Cancer Res. 2006, 66, 4795–4801. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, X.; Riley, T.; Levine, A.J. The regulation of the endosomal compartment by p53 the tumor suppressor gene. Febs. J. 2009, 276, 2201–2212. [Google Scholar] [CrossRef] [PubMed]
- Vietri, M.; Radulovic, M.; Stenmark, H. The many functions of ESCRTs. Nat. Rev. Mol. Cell Biol. 2020, 21, 25–42. [Google Scholar] [CrossRef] [PubMed]
- Cooks, T.; Pateras, I.S.; Jenkins, L.M.; Patel, K.M.; Robles, A.I.; Morris, J.; Forshew, T.; Appella, E.; Gorgoulis, V.; Harris, C.C. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat. Commun. 2018, 9, 1–15. [Google Scholar] [CrossRef] [Green Version]
- Hallal, S.; Mallawaaratchy, D.M.; Wei, H.; Ebrahimkhani, S.; Stringer, B.W.; Day, B.W.; Boyd, A.W.; Guillemin, G.; Buckland, M.E.; Kaufman, K.L. Extracellular Vesicles Released by Glioblastoma Cells Stimulate Normal Astrocytes to Acquire a Tumor-Supportive Phenotype Via p53 and MYC Signaling Pathways. Mol. Neurobiol. 2019, 56, 4566–4581. [Google Scholar] [CrossRef] [Green Version]
- Pazzaglia, E.U.; Pringle, A.J. The role of macrophages and giant cells in loosening of joint replacement. Arch. Orthop. Trauma. Surgery 1988, 107, 20–26. [Google Scholar] [CrossRef] [Green Version]
- Cappellesso, R.; Tinazzi, A.; Giurici, T.; Simonato, F.; Guzzardo, V.; Ventura, L.; Crescenzi, M.; Chiarelli, S.; Fassina, A. Programmed cell death 4 and microRNA 21 inverse expression is maintained in cells and exosomes from ovarian serous carcinoma effusions. Cancer Cytopathol. 2014, 122, 685–693. [Google Scholar] [CrossRef]
- Chen, W.-X.; Liu, X.-M.; Lv, M.-M.; Chen, L.; Zhao, J.-H.; Zhong, S.-L.; Ji, M.-H.; Hu, Q.; Luo, Z.; Wu, J.-Z.; et al. Exosomes from drug-resistant breast cancer cells transmit chemoresistance by a horizontal transfer of MicroRNAs. PLoS ONE 2014, 9, e95240. [Google Scholar] [CrossRef]
- Liu, T.; Chen, G.; Sun, D.; Lei, M.; Li, Y.; Zhou, C.; Li, X.; Xue, W.; Wang, H.; Liu, C.; et al. Exosomes containing miR-21 transfer the characteristic of cisplatin resistance by targeting PTEN and PDCD4 in oral squamous cell carcinoma. Acta Biochim. Biophys. Sin. 2017, 49, 808–816. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allegra, A.; Ettari, R.; Innao, V.; Bitto, A. Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma. Cells 2021, 10, 448. [Google Scholar] [CrossRef]
- Wang, J.; Hendrix, A.; Hernot, S.; Lemaire, M.; De Bruyne, E.; Van Valckenborgh, E.; Lahoutte, T.; De Wever, O.; Vanderkerken, K.; Menu, E. Bone marrow stromal cell–derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood 2014, 124, 555–566. [Google Scholar] [CrossRef] [Green Version]
- Khan, S.; Jutzy, J.M.S.; Aspe, J.R.; McGregor, D.W.; Neidigh, J.W.; Wall, N.R. Survivin is released from cancer cells via exosomes. Apoptosis 2010, 16, 1–12. [Google Scholar] [CrossRef] [Green Version]
- Qu, J.L.; Qu, X.J.; Qu, J.L.; Qu, X.J.; Zhao, M.F.; Teng, Y.E.; Zhang, Y.; Hou, K.Z.; Jiang, Y.H.; Yang, X.H.; et al. The role of cbl family of ubiquitin ligases in gastric cancer exosome-induced apoptosis of Jurkat T cells. Acta Oncol. 2009, 48, 1173–1180. [Google Scholar] [CrossRef] [Green Version]
- Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 1965, 37, 614–636. [Google Scholar] [CrossRef]
- Al-Mayah, A.H.J.; Bright, S.J.; Bowler, D.A.; Slijepcevic, P.; Goodwin, E.; Kadhim, M.A. Exosome-Mediated Telomere Instability in Human Breast Epithelial Cancer Cells after X Irradiation. Radiat. Res. 2017, 187, 98–106. [Google Scholar] [CrossRef] [PubMed]
- Bhandari, V.; Hoey, C.; Liu, L.Y.; Lalonde, E.; Ray, J.; Livingstone, J.; Lesurf, R.; Shiah, Y.J.; Vujcic, T.; Huang, X.; et al. Molecular landmarks of tumor hypoxia across cancer types. Nat. Genet. 2019, 51, 308–318. [Google Scholar] [CrossRef]
- Ohyashiki, J.H.; Umezu, T.; Ohyashiki, K. Exosomes promote bone marrow angiogenesis in hematologic neoplasia: The role of hypoxia. Curr. Opin. Hematol. 2016, 23. [Google Scholar] [CrossRef]
- Shao, C.; Yang, F.; Miao, S.; Liu, W.; Wang, C.; Shu, Y.; Shen, H. Role of hypoxia-induced exosomes in tumor biology. Mol. Cancer 2018, 17, 1–8. [Google Scholar] [CrossRef]
- Huang, Z.; Feng, Y. Exosomes Derived From Hypoxic Colorectal Cancer Cells Promote Angiogenesis Through Wnt4-Induced β-Catenin Signaling in Endothelial Cells. Oncol. Res. Featur. Preclin. Clin. Cancer Ther. 2017, 25, 651–661. [Google Scholar] [CrossRef]
- Hsu, Y.-L.; Hung, J.-Y.; Chang, W.-A.; Lin, Y.-S.; Pan, Y.-C.; Tsai, P.-H.; Wu, C.-Y.; Kuo, P.-L. Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1. Oncogene 2017, 36, 4929–4942. [Google Scholar] [CrossRef]
- Tadokoro, H.; Umezu, T.; Ohyashiki, K.; Hirano, T.; Ohyashiki, J.H. Exosomes derived from hypoxic leukemia cells enhance tube formation in endothelial cells. J. Biol. Chem. 2013, 288, 34343–34351. [Google Scholar] [CrossRef] [Green Version]
- Yang, H.; Zhang, H.; Ge, S.; Ning, T.; Bai, M.; Li, J.; Li, S.; Sun, W.; Deng, T.; Zhang, L.; et al. Exosome-Derived miR-130a Activates Angiogenesis in Gastric Cancer by Targeting C-MYB in Vascular Endothelial Cells. Mol. Ther. 2018, 26, 2466–2475. [Google Scholar] [CrossRef] [Green Version]
- He, L.; Zhu, W.; Chen, Q.; Yuan, Y.; Wang, Y.; Wang, J.; Wu, X. Ovarian cancer cell-secreted exosomal miR-205 promotes metastasis by inducing angiogenesis. Theranostics 2019, 9, 8206–8220. [Google Scholar] [CrossRef] [PubMed]
- Shang, D.; Xie, C.; Hu, J.; Tan, J.; Yuan, Y.; Liu, Z.; Yang, Z. Pancreatic cancer cell–derived exosomal microRNA-27a promotes angiogenesis of human microvascular endothelial cells in pancreatic cancer via BTG2. J. Cell. Mol. Med. 2020, 24, 588–604. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Müller, H.; Hu, J.; Popp, R.; Schmidt, M.H.; Müller-Decker, K.; Mollenhauer, J.; Fisslthaler, B.; Eble, J.A.; Fleming, I. Deleted in Malignant Brain Tumors 1 is Present in the Vascular Extracellular Matrix and Promotes Angiogenesis. Arter. Thromb. Vasc. Biol. 2012, 32, 442–448. [Google Scholar] [CrossRef] [Green Version]
- Lucero, R.; Zappulli, V.; Sammarco, A.; Murillo, O.D.; Cheah, P.S.; Srinivasan, S.; Tai, E.; Ting, D.T.; Wei, Z.; Roth, M.E.; et al. Glioma-Derived miRNA-Containing Extracellular Vesicles Induce Angiogenesis by Reprogramming Brain Endothelial Cells. Cell Rep. 2020, 30, 2065–2074.e4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kucharzewska, P.; Christianson, H.C.; Welch, J.E.; Svensson, K.J.; Fredlund, E.; Ringnér, M.; Mörgelin, M.; Bourseau-Guilmain, E.; Bengzon, J.; Belting, M. Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc. Natl. Acad. Sci. USA 2013, 110, 7312–7317. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Giusti, I.; Delle Monache, S.; Di Francesco, M.; Sanità, P.; D’Ascenzo, S.; Gravina, G.L.; Festuccia, C.; Dolo, V. From glioblastoma to endothelial cells through extracellular vesicles: Messages for angiogenesis. Tumor Biol. 2016, 37, 12743–12753. [Google Scholar] [CrossRef] [PubMed]
- Gesierich, S.; Berezovskiy, I.; Ryschich, E.; Zöller, M. Systemic Induction of the Angiogenesis Switch by the Tetraspanin D6.1A/CO-029. Cancer Res. 2006, 66, 7083–7094. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nazarenko, I.; Rana, S.; Baumann, A.; McAlear, J.; Hellwig, A.; Trendelenburg, M.; Lochnit, G.; Preissner, K.T.; Zöller, M. Cell Surface Tetraspanin Tspan8 Contributes to Molecular Pathways of Exosome-Induced Endothelial Cell Activation. Cancer Res. 2010, 70, 1668–1678. [Google Scholar] [CrossRef] [Green Version]
- Verweij, F.J.; van Eijndhoven, M.A.; Hopmans, E.S.; Vendrig, T.; Wurdinger, T.; Cahir-McFarland, E.; Kieff, E.; Geerts, D.; van der Kant, R.; Neefjes, J.; et al. LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation. Embo J. 2011, 30, 2115–2129. [Google Scholar] [CrossRef]
- Tkach, M.; Théry, C. Communication by Extracellular Vesicles: Where We Are and Where We Need to Go. Cell 2016, 164, 1226–1232. [Google Scholar] [CrossRef] [Green Version]
- El Kharbili, M.; Robert, C.; Witkowski, T.; Danty-Berger, E.; Barbollat-Boutrand, L.; Masse, I.; Gadot, N.; de la Fouchardiere, A.; McDonald, P.C.; Dedhar, S.; et al. Tetraspanin 8 is a novel regulator of ILK-driven β1 integrin adhesion and signaling in invasive melanoma cells. Oncotarget 2017, 8, 17140–17155. [Google Scholar] [CrossRef] [Green Version]
- Grosshans, C.A.; Cech, T.R. Metal ion requirements for sequence-specific endoribonuclease activity of the Tetrahymena ribozyme. Biochemistry 1989, 28, 6888–6894. [Google Scholar] [CrossRef]
- Segura, E.; Guérin, C.; Hogg, N.; Amigorena, S.; Théry, C. CD8+Dendritic Cells Use LFA-1 to Capture MHC-Peptide Complexes from Exosomes In Vivo. J. Immunol. 2007, 179, 1489–1496. [Google Scholar] [CrossRef] [Green Version]
- Ko, S.Y.; Lee, W.; Kenny, H.A.; Dang, L.H.; Ellis, L.M.; Jonasch, E.; Lengyel, E.; Naora, H. Cancer-derived small extracellular vesicles promote angiogenesis by heparin-bound, bevacizumab-insensitive VEGF, independent of vesicle uptake. Commun. Biol. 2019, 2, 1–17. [Google Scholar] [CrossRef] [Green Version]
- Dillekås, H.; Rogers, M.; Straume, O. Are 90% of deaths from cancer caused by metastases? Cancer Med. 2019, 8, 5574–5576. [Google Scholar] [CrossRef] [Green Version]
- Hao, S.; Ye, Z.; Li, F.; Meng, Q.; Qureshi, M.; Yang, J.; Xiang, J. Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. Exp. Oncol. 2006, 28, 126–131. [Google Scholar]
- McCready, J.; Sims, J.D.; Chan, D.; Jay, D.G. Secretion of extracellular hsp90α via exosomes increases cancer cell motility: A role for plasminogen activation. BMC Cancer 2010, 10, 294. [Google Scholar] [CrossRef] [Green Version]
- Higginbotham, J.N.; Beckler, M.D.; Gephart, J.D.; Franklin, J.L.; Bogatcheva, G.; Kremers, G.-J.; Piston, D.W.; Ayers, G.D.; McConnell, R.E.; Tyska, M.J.; et al. Amphiregulin Exosomes Increase Cancer Cell Invasion. Curr. Biol. 2011, 21, 779–786. [Google Scholar] [CrossRef] [Green Version]
- Aga, M.; Bentz, G.L.; Raffa, S.; Torrisi, M.R.; Kondo, S.; Wakisaka, N.; Yoshizaki, T.; Pagano, J.S.; Shackelford, J. Exosomal HIF1α supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes. Oncogene 2014, 33, 4613–4622. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Corcoran, C.; Rani, S.; O’Driscoll, L.; O’Brien, K.; O’Neill, A.; Prencipe, M.; Sheikh, R.; Webb, G.; McDermott, R.; Watson, W.; et al. Docetaxel-resistance in prostate cancer: Evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS ONE 2012, 7, e50999. [Google Scholar] [CrossRef] [PubMed]
- Guo, D.; Lui, G.Y.L.; Lai, S.L.; Wilmott, J.S.; Tikoo, S.; Jackett, L.A.; Quek, C.; Brown, D.L.; Sharp, D.M.; Kwan, R.Y.Q.; et al. RAB27A promotes melanoma cell invasion and metastasis via regulation of pro-invasive exosomes. Int. J. Cancer 2019, 144, 3070–3085. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bijnsdorp, I.V.; Geldof, A.A.; Lavaei, M.; Piersma, S.R.; Van Moorselaar, R.J.A.; Jimenez, C.R. Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients. J. Extracell. Vesicles 2013, 2, 1–10. [Google Scholar] [CrossRef]
- Sung, B.H.; Ketova, T.; Hoshino, D.; Zijlstra, A.; Weaver, A.M. Directional cell movement through tissues is controlled by exosome secretion. Nat. Commun. 2015, 6, 7164. [Google Scholar] [CrossRef] [Green Version]
- Di Vizio, D.; Morello, M.; Dudley, A.C.; Schow, P.W.; Adam, R.M.; Morley, S.; Mulholland, D.; Rotinen, M.; Hager, M.H.; Insabato, L.; et al. Large Oncosomes in Human Prostate Cancer Tissues and in the Circulation of Mice with Metastatic Disease. Am. J. Pathol. 2012, 181, 1573–1584. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Gu, Y.; Han, Y.; Zhang, Q.; Jiang, Z.; Zhang, X.; Huang, B.; Xu, X.; Zheng, J.; Cao, X. Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils. Cancer Cell 2016, 30, 243–256. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhou, W.; Fong, M.Y.; Min, Y.; Somlo, G.; Liu, L.; Palomares, M.R.; Yu, Y.; Chow, A.; O’Connor, S.T.F.; Chin, A.R.; et al. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell 2014, 25, 501–515. [Google Scholar] [CrossRef] [Green Version]
- Peinado, H.; Aleckovic, M.; Lavotshkin, S.; Matei, I.; Costa-Silva, B.; Moreno-Bueno, G.; Hergueta-Redondo, M.; Williams, C.; Garcia-Santos, G.; Ghajar, C.; et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 2012, 18, 883–891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bigagli, E.; Luceri, C.; Guasti, D.; Cinci, L. Exosomes secreted from human colon cancer cells influence the adhesion of neighboring metastatic cells: Role of microRNA-210. Cancer Biol. Ther. 2016, 17, 1062–1069. [Google Scholar] [CrossRef] [Green Version]
- Hood, J.L.; San, R.S.; Wickline, S.A. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011, 71, 3792–3801. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kinzler, K.W.; Vogelstein, B. Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 1997, 386, 761–763. [Google Scholar] [CrossRef] [PubMed]
- Negrini, S.; Gorgoulis, V.G.; Halazonetis, T.D. Genomic instability--an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 2010, 11, 220–228. [Google Scholar] [CrossRef]
- Pal, T.; Permuth-Wey, J.; Sellers, T.A. A review of the clinical relevance of mismatch-repair deficiency in ovarian cancer. Cancer 2008, 113, 733–742. [Google Scholar] [CrossRef] [Green Version]
- Tarsounas, M.; Sung, P. The antitumorigenic roles of BRCA1–BARD1 in DNA repair and replication. Nat. Rev. Mol. Cell Biol. 2020, 21, 284–299. [Google Scholar] [CrossRef]
- Wu, J.; Lu, L.-Y.; Yu, X. The role of BRCA1 in DNA damage response. Protein Cell 2010, 1, 117–123. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abdouh, M.; Floris, M.; Gao, Z.-H.; Arena, V.; Arena, M.; Arena, G.O. Colorectal cancer-derived extracellular vesicles induce transformation of fibroblasts into colon carcinoma cells. J. Exp. Clin. Cancer Res. 2019, 38, 1–22. [Google Scholar] [CrossRef] [PubMed]
- Tsering, T.; Laskaris, A.; Abdouh, M.; Bustamante, P.; Parent, S.; Jin, E.; Ferrier, S.T.; Arena, G.; Burnier, J.V. Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation. Cancers 2020, 12, 2923. [Google Scholar] [CrossRef] [PubMed]
- Momen-Heravi, F.; Bala, S. Extracellular vesicles in oral squamous carcinoma carry oncogenic miRNA profile and reprogram monocytes via NF-κB pathway. Oncotarget 2018, 9, 34838–34854. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, L.; Zhang, X.; Zhang, B.; Shi, H.; Yuan, X.; Sun, Y.; Pan, Z.; Qian, H.; Xu, W. Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression. Tumour Biol. 2016, 37, 12169–12180. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Wang, S.; Zhu, R.; Li, H.; Han, Q.; Zhao, R.C. Lung tumor exosomes induce a pro-inflammatory phenotype in mesenchymal stem cells via NFκB-TLR signaling pathway. J. Hematol. Oncol. 2016, 9, 42. [Google Scholar] [CrossRef] [Green Version]
- Pritchard, A.; Tousif, S.; Wang, Y.; Hough, K.; Khan, S.; Strenkowski, J.; Chacko, B.K.; Darley-Usmar, V.M.; Deshane, J.S. Lung Tumor Cell-Derived Exosomes Promote M2 Macrophage Polarization. Cells 2020, 9, 1303. [Google Scholar] [CrossRef] [PubMed]
- Lehuédé, C.; Dupuy, F.; Rabinovitch, R.; Jones, R.G.; Siegel, P.M. Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis. Cancer Res. 2016, 76, 5201–5208. [Google Scholar] [CrossRef] [Green Version]
- Cardone, R.A.; Casavola, V.; Reshkin, S.J. The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis. Nat. Rev. Cancer 2005, 5, 786–795. [Google Scholar] [CrossRef] [PubMed]
- Parolini, I.; Federici, C.; Raggi, C.; Lugini, L.; Palleschi, S.; De Milito, A.; Coscia, C.; Iessi, E.; Logozzi, M.; Molinari, A.; et al. Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells. J. Biol. Chem. 2009, 284, 34211–34222. [Google Scholar] [CrossRef] [Green Version]
- Fong, M.Y.; Zhou, W.; Liu, L.; Alontaga, A.Y.; Chandra, M.; Ashby, J.; Chow, A.; O’Connor, S.T.F.; Li, S.; Chin, A.R.; et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat. Cell Biol. 2015, 17, 183–194. [Google Scholar] [CrossRef] [Green Version]
- Lázaro-Ibáñez, E.; Lunavat, T.R.; Jang, S.C.; Escobedo-Lucea, C.; La Cruz, J.O.-D.; Siljander, P.; Lötvall, J.; Yliperttula, M. Distinct prostate cancer-related mRNA cargo in extracellular vesicle subsets from prostate cell lines. BMC Cancer 2017, 17, 1–11. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lazar, I.; Clement, E.; Dauvillier, S.; Milhas, D.; Ducoux-Petit, M.; Legonidec, S.; Moro, C.; Soldan, V.; Dalle, S.; Balor, S.; et al. Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer. Cancer Res. 2016, 76, 4051–4057. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, B.; Yin, Y.; Lai, R.C.; Lim, S.K. Immunotherapeutic potential of extracellular vesicles. Front. Immunol. 2014, 5, 518. [Google Scholar] [CrossRef] [Green Version]
- Whiteside, T.L. Exosomes and tumor-mediated immune suppression. J. Clin. Investig. 2016, 126, 1216–1223. [Google Scholar] [CrossRef] [Green Version]
- Wieckowski, E.U.; Visus, C.; Szajnik, M.; Szczepanski, M.J.; Storkus, W.; Whiteside, T.L. Tumor-Derived Microvesicles Promote Regulatory T Cell Expansion and Induce Apoptosis in Tumor-Reactive Activated CD8+ T Lymphocytes. J. Immunol. 2009, 183, 3720–3730. [Google Scholar] [CrossRef] [Green Version]
- Ning, Y.; Shen, K.; Wu, Q.; Sun, X.; Bai, Y.; Xie, Y.; Pan, J.; Qi, C. Tumor exosomes block dendritic cells maturation to decrease the T cell immune response. Immunol. Lett. 2018, 199, 36–43. [Google Scholar] [CrossRef]
- Hedlund, M.; Nagaeva, O.; Kargl, D.; Baranov, V.; Mincheva-Nilsson, L. Thermal- and Oxidative Stress Causes Enhanced Release of NKG2D Ligand-Bearing Immunosuppressive Exosomes in Leukemia/Lymphoma T and B Cells. PLoS ONE 2011, 6, e16899. [Google Scholar] [CrossRef]
- Lundholm, M.; Schröder, M.; Nagaeva, O.; Baranov, V.; Widmark, A.; Mincheva-Nilsson, L.; Wikström, P. Prostate Tumor-Derived Exosomes Down-Regulate NKG2D Expression on Natural Killer Cells and CD8+ T Cells: Mechanism of Immune Evasion. PLoS ONE 2014, 9, e108925. [Google Scholar] [CrossRef]
- Liu, Y.; Gu, Y.; Cao, X. The exosomes in tumor immunity. OncoImmunology 2015, 4, e1027472. [Google Scholar] [CrossRef] [Green Version]
- Hong, C.-S.; Sharma, P.; Yerneni, S.S.; Simms, P.; Jackson, E.K.; Whiteside, T.L.; Boyiadzis, M. Circulating exosomes carrying an immunosuppressive cargo interfere with cellular immunotherapy in acute myeloid leukemia. Sci. Rep. 2017, 7, 1–10. [Google Scholar] [CrossRef] [Green Version]
- Zhao, J.; Schlößer, H.; Wang, Z.; Qin, J.; Li, J.; Popp, F.C.; Popp, M.C.; Alakus, H.; Chon, S.-H.; Hansen, H.P.; et al. Tumor-derived extracellular vesicles inhibit natural killer cell function in pancreatic cancer. Cancers 2019, 11, 874. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sharma, P.; Diergaarde, B.; Ferrone, S.; Kirkwood, J.M.; Whiteside, T.L. Melanoma cell-derived exosomes in plasma of melanoma patients suppress functions of immune effector cells. Sci. Rep. 2020, 10, 1–11. [Google Scholar] [CrossRef]
- Batista, I.; Quintas, S.; Melo, S. The Interplay of Exosomes and NK Cells in Cancer Biology. Cancers 2021, 13, 473. [Google Scholar] [CrossRef]
- Anderson, H.C.; Mulhall, D.; Garimella, R. Role of extracellular membrane vesicles in the pathogenesis of various diseases, including cancer, renal diseases, atherosclerosis, and arthritis. Lab. Investig. 2010, 90, 1549–1557. [Google Scholar] [CrossRef] [PubMed]
- Tripisciano, C.; Weiss, R.; Eichhorn, T.; Spittler, A.; Heuser, T.; Fischer, M.B.; Weber, V. Different Potential of Extracellular Vesicles to Support Thrombin Generation: Contributions of Phosphatidylserine, Tissue Factor, and Cellular Origin. Sci. Rep. 2017, 7, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Steidel, C.; Ender, F.; Rody, A.; von Bubnoff, N.; Gieseler, F. Biologically Active Tissue Factor-Bearing Larger Ectosome-Like Extracellular Vesicles in Malignant Effusions from Ovarian Cancer Patients: Correlation with Incidence of Thrombosis. Int. J. Mol. Sci. 2021, 22, 790. [Google Scholar] [CrossRef] [PubMed]
- Prandoni, P.; Falanga, A.; Piccioli, A. Cancer and venous thromboembolism. Lancet Oncol. 2005, 6, 401–410. [Google Scholar] [CrossRef]
- Grilz, E.; Königsbrügge, O.; Posch, F.; Schmidinger, M.; Pirker, R.; Lang, I.M.; Pabinger, I.; Ay, C. Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer. Haematologica 2018, 103, 1549–1556. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, X.; Qiao, D.; Chen, L.; Xu, M.; Chen, S.; Huang, L.; Wang, F.; Chen, Z.; Cai, J.; Fu, L. Chemotherapeutic drugs stimulate the release and recycling of extracellular vesicles to assist cancer cells in developing an urgent chemoresistance. Mol. Cancer 2019, 18, 1–18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Osataphan, S.; Patell, R.; Chiasakul, T.; Khorana, A.A.; Zwicker, J.I. Extended thromboprophylaxis for medically ill patients with cancer: A systemic review and meta-analysis. Blood Adv. 2021, 5, 2055–2062. [Google Scholar] [CrossRef] [PubMed]
- Shah, S.; Karathanasi, A.; Revythis, A.; Ioannidou, E.; Boussios, S. Cancer-Associated Thrombosis: A New Light on an Old Story. Diseases 2021, 9, 34. [Google Scholar] [CrossRef] [PubMed]
- Tesselaar, M.E.T.; Romijn, F.P.H.T.M.; Van Der Linden, I.K.; Prins, F.A.; Bertina, R.M.; Osanto, S. Microparticle-associated tissue factor activity: A link between cancer and thrombosis? J. Thromb. Haemost. 2007, 5, 520–527. [Google Scholar] [CrossRef]
- Gardiner, C.; Harrison, P.; Belting, M.; Böing, A.; Campello, E.; Carter, B.S.; Collier, M.E.; Coumans, F.; Ettelaie, C.; Van Es, N.; et al. Extracellular vesicles, tissue factor, cancer and thrombosis–discussion themes of the ISEV 2014 Educational Day. J. Extracell. Vesicles 2015, 4, 26901. [Google Scholar] [CrossRef] [Green Version]
- Dávila, M.; Amirkhosravi, A.; Coll, E.; Desai, H.; Robles, L.; Colon, J.; Baker, C.H.; Francis, J.L. Tissue factor-bearing microparticles derived from tumor cells: Impact on coagulation activation. J. Thromb. Haemost. 2008, 6, 1517–1524. [Google Scholar] [CrossRef]
- Thomas, G.; Panicot-Dubois, L.; Lacroix, R.; Dignat-George, F.; Lombardo, D.; Dubois, C. Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo. J. Exp. Med. 2009, 206, 1913–1927. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.-G.; Geddings, J.E.; Aleman, M.M.; Cardenas, J.C.; Chantrathammachart, P.; Williams, J.C.; Kirchhofer, D.; Bogdanov, V.; Bach, R.R.; Rak, J.; et al. Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer. Blood 2012, 119, 5543–5552. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Thomas, G.M.; Brill, A.; Mezouar, S.; Crescence, L.; Gallant, M.; Dubois, C.; Wagner, D.D. Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice. J. Thromb. Haemost. 2015, 13, 1310–1319. [Google Scholar] [CrossRef]
- Hisada, Y.; Ay, C.; Auriemma, A.C.; Cooley, B.C.; Mackman, N. Human pancreatic tumors grown in mice release tissue factor-positive microvesicles that increase venous clot size. J. Thromb. Haemost. 2017, 15, 2208–2217. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gheldof, D.; Mullier, F.; Bailly, N.; Devalet, B.; Dogné, J.-M.; Chatelain, B.; Chatelain, C. Microparticle bearing tissue factor: A link between promyelocytic cells and hypercoagulable state. Thromb. Res. 2014, 133, 433–439. [Google Scholar] [CrossRef]
- Nielsen, T.; Kristensen, S.R.; Gregersen, H.; Teodorescu, E.M.; Christiansen, G.; Pedersen, S. Extracellular vesicle-associated procoagulant phospholipid and tissue factor activity in multiple myeloma. PLoS ONE 2019, 14, e0210835. [Google Scholar] [CrossRef]
- Rousseau, A.; Van Dreden, P.; Khaterchi, A.; Larsen, A.K.; Elalamy, I.; Gerotziafas, G.T. Procoagulant microparticles derived from cancer cells have determinant role in the hypercoagulable state associated with cancer. Int. J. Oncol. 2017, 51, 1793–1800. [Google Scholar] [CrossRef]
- Madan, E.; Pelham, C.J.; Nagane, M.; Parker, T.M.; Marques, R.C.; Fazio, K.; Shaik, K.; Yuan, Y.; Henriques, V.; Galzerano, A.; et al. Flower isoforms promote competitive growth in cancer. Nat. Cell Biol. 2019, 572, 260–264. [Google Scholar] [CrossRef] [PubMed]
- Bowling, S.; Di Gregorio, A.; Sancho, M.; Pozzi, S.; Aarts, M.; Signore, M.; Schneider, M.D.; Martinez-Barbera, J.P.; Gil, J.; Rodríguez, T.A. P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development. Nat. Commun. 2018, 9, 1763. [Google Scholar] [CrossRef] [PubMed]
- Wu, B.; Sun, D.; Ma, L.; Deng, Y.; Zhang, S.; Dong, L.; Chen, S. Exosomes isolated from CAPS1-overexpressing colorectal cancer cells promote cell migration. Oncol. Rep. 2019, 42, 2528–2536. [Google Scholar] [CrossRef] [PubMed]
- Sato, Y.; Ochiai, S.; Murata, T.; Kanda, T.; Goshima, F.; Kimura, H. Elimination of LMP1-expressing cells from a monolayer of gastric cancer AGS cells. Oncotarget 2017, 8, 39345–39355. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boopathy, G.T.K.; Hong, W. Role of Hippo Pathway-YAP/TAZ Signaling in Angiogenesis. Front. Cell Dev. Biol. 2019, 7, 49. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Yee, P.P.; Wei, Y.; Liu, Z.; Kawasawa, Y.I.; Li, W. Differential YAP expression in glioma cells induces cell competition and promotes tumorigenesis. J. Cell Sci. 2019, 132, jcs225714. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, M.; Zhao, X.; Qiu, R.; Gong, Z.; Huang, F.; Yu, W.; Shen, B.; Sha, X.; Dong, H.; Huang, J.; et al. Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a. Oncogene 2021, 40, 2296–2308. [Google Scholar] [CrossRef]
- He, X.; Saint-Jeannet, J.-P.; Wang, Y.; Nathans, J.; Dawid, I.; Varmus, H. A Member of the Frizzled Protein Family Mediating Axis Induction by Wnt-5A. Science 1997, 275, 1652–1654. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Katoh, M. WNT/PCP signaling pathway and human cancer (Review). Oncol. Rep. 2005, 14, 1583–1588. [Google Scholar] [CrossRef]
- Luga, V.; Zhang, L.; Viloria-Petit, A.M.; Ogunjimi, A.A.; Inanlou, M.R.; Chiu, E.; Buchanan, M.; Hosein, A.N.; Basik, M.; Wrana, J.L. Exosomes Mediate Stromal Mobilization of Autocrine Wnt-PCP Signaling in Breast Cancer Cell Migration. Cell 2012, 151, 1542–1556. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Longley, D.B.; Johnston, P.G. Molecular mechanisms of drug resistance. J. Pathol. 2005, 205, 275–292. [Google Scholar] [CrossRef]
- Holohan, C.; Van Schaeybroeck, S.; Longley, D.B.; Johnston, P.G. Cancer drug resistance: An evolving paradigm. Nat. Rev. Cancer 2013, 13, 714–726. [Google Scholar] [CrossRef] [PubMed]
- Rijpma, S.R.; Heuvel, J.J.M.W.V.D.; Van Der Velden, M.; Sauerwein, R.W.; Russel, F.G.M.; Koenderink, J.B. Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity. Malar. J. 2014, 13, 359. [Google Scholar] [CrossRef] [Green Version]
- Shedden, K.; Xie, X.T.; Chandaroy, P.; Chang, Y.T.; Rosania, G.R. Expulsion of small molecules in vesicles shed by cancer cells: Association with gene expression and chemosensitivity profiles. Cancer Res. 2003, 63, 4331–4337. [Google Scholar] [PubMed]
- Koch, R.; Aung, T.; Vogel, D.; Chapuy, B.; Wenzel, D.; Becker, S.; Sinzig, U.; Venkataramani, V.; Von Mach, T.; Jacob, R.; et al. Nuclear Trapping through Inhibition of Exosomal Export by Indomethacin Increases Cytostatic Efficacy of Doxorubicin and Pixantrone. Clin. Cancer Res. 2016, 22, 395–404. [Google Scholar] [CrossRef] [Green Version]
- Safaei, R.; Larson, B.J.; Cheng, T.C.; Gibson, M.A.; Otani, S.; Naerdemann, W.; Howell, S.B. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol. Cancer Ther. 2005, 4, 1595–1604. [Google Scholar] [CrossRef] [Green Version]
- Federici, C.; Petrucci, F.; Caimi, S.; Cesolini, A.; Logozzi, M.; Borghi, M.; D’Ilio, S.; Lugini, L.; Violante, N.; Azzarito, T.; et al. Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. PLoS ONE 2014, 9, e88193. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pascucci, L.; Coccè, V.; Bonomi, A.; Ami, D.; Ceccarelli, P.; Ciusani, E.; Viganò, L.; Locatelli, A.; Sisto, F.; Doglia, S.M.; et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery. J. Control. Release 2014, 192, 262–270. [Google Scholar] [CrossRef]
- Bebawy, M.; Combes, V.; Lee, E.; Jaiswal, R.; Gong, J.; Bonhoure, A.; Grau, G.E.R. Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia 2009, 23, 1643–1649. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Torreggiani, E.; Roncuzzi, L.; Perut, F.; Zini, N.; Baldini, N. Multimodal transfer of MDR by exosomes in human osteosarcoma. Int. J. Oncol. 2016, 49, 189–196. [Google Scholar] [CrossRef] [Green Version]
- Bhattacharya, S.; Pal, K.; Sharma, A.; Dutta, S.K.; Lau, J.S.; Yan, I.K.; Wang, E.; Elkhanany, A.; Alkharfy, K.M.; Sanyal, A.; et al. GAIP Interacting Protein C-Terminus Regulates Autophagy and Exosome Biogenesis of Pancreatic Cancer through Metabolic Pathways. PLoS ONE 2014, 9, e114409. [Google Scholar] [CrossRef] [PubMed]
- Qu, Z.; Wu, J.; Wu, J.; Luo, D.; Jiang, C.; Ding, Y. Exosomes derived from HCC cells induce sorafenib resistance in hepatocellular carcinoma both in vivo and in vitro. J. Exp. Clin. Cancer Res. 2016, 35, 1–12. [Google Scholar] [CrossRef] [Green Version]
- Ozawa, P.M.M.; Alkhilaiwi, F.; Cavalli, I.J.; Malheiros, D.; Ribeiro, E.M.D.S.F.; Cavalli, L.R. Extracellular vesicles from triple-negative breast cancer cells promote proliferation and drug resistance in non-tumorigenic breast cells. Breast Cancer Res. Treat. 2018, 172, 713–723. [Google Scholar] [CrossRef] [PubMed]
- Vella, L.J.; Behren, A.; Coleman, B.; Greening, D.W.; Hill, A.; Cebon, J. Intercellular Resistance to BRAF Inhibition Can Be Mediated by Extracellular Vesicle–Associated PDGFRβ. Neoplasia 2017, 19, 932–940. [Google Scholar] [CrossRef]
- Uchihara, T.; Miyake, K.; Yonemura, A.; Komohara, Y.; Itoyama, R.; Koiwa, M.; Yasuda, T.; Arima, K.; Harada, K.; Eto, K.; et al. Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance. Cancer Res. 2020, 80, 3222–3235. [Google Scholar] [CrossRef]
- Maacha, S.; Bhat, A.A.; Jimenez, L.; Raza, A.; Haris, M.; Uddin, S.; Grivel, J.-C. Extracellular vesicles-mediated intercellular communication: Roles in the tumor microenvironment and anti-cancer drug resistance. Mol. Cancer 2019, 18, 1–16. [Google Scholar] [CrossRef] [Green Version]
- Kreger, B.T.; Johansen, E.R.; Cerione, R.A.; Antonyak, M.A. The Enrichment of Survivin in Exosomes from Breast Cancer Cells Treated with Paclitaxel Promotes Cell Survival and Chemoresistance. Cancers 2016, 8, 111. [Google Scholar] [CrossRef] [Green Version]
- Yang, Z.; Zhao, N.; Cui, J.; Wu, H.; Xiong, J.; Peng, T. Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210. Cell. Oncol. 2020, 43, 123–136. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aung, T.; Chapuy, B.; Vogel, D.; Wenzel, D.; Oppermann, M.; Lahmann, M.; Weinhage, T.; Menck, K.; Hupfeld, T.; Koch, R.; et al. Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3. Proc. Natl. Acad. Sci. USA 2011, 108, 15336–15341. [Google Scholar] [CrossRef] [Green Version]
- Ciravolo, V.; Huber, V.; Ghedini, G.C.; Venturelli, E.; Bianchi, F.; Campiglio, M.; Morelli, D.; Villa, A.; Della Mina, P.; Menard, S.; et al. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J. Cell. Physiol. 2012, 227, 658–667. [Google Scholar] [CrossRef]
- Lubin, A.J.; Zhang, R.R.; Kuo, J.S. Extracellular Vesicles Containing PD-L1 Contribute to Immune Evasion in Glioblastoma. Neurosurgery 2018, 83, E98–E100. [Google Scholar] [CrossRef] [Green Version]
- Lara, P.; Chan, A.; Cruz, L.; Quest, A.; Kogan, M. Exploiting the Natural Properties of Extracellular Vesicles in Targeted Delivery towards Specific Cells and Tissues. Pharmaceutics 2020, 12, 1022. [Google Scholar] [CrossRef] [PubMed]
- Katakowski, M.; Buller, B.; Zheng, X.; Lu, Y.; Rogers, T.; Osobamiro, O.; Shu, W.; Jiang, F.; Chopp, M. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett. 2013, 335, 201–204. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lara, P.; Palma-Florez, S.; Salas-Huenuleo, E.; Polakovicova, I.; Guerrero, S.; Lobos-Gonzalez, L.; Campos, A.; Muñoz, L.; Jorquera-Cordero, C.; Varas-Godoy, M.; et al. Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors. J. Nanobiotechnol. 2020, 18, 1–17. [Google Scholar] [CrossRef] [Green Version]
- Wiklander, O.P.B.; Nordin, J.Z.; O’Loughlin, A.; Gustafsson, Y.; Corso, G.; Mäger, I.; Vader, P.; Lee, Y.; Sork, H.; Seow, Y.; et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J. Extracell. Vesicles 2015, 4, 26316. [Google Scholar] [CrossRef] [Green Version]
- Yang, T.; Martin, P.; Fogarty, B.; Brown, A.; Schurman, K.; Phipps, R.; Yin, V.P.; Lockman, P.; Bai, S. Exosome Delivered Anticancer Drugs Across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio. Pharm. Res. 2015, 32, 2003–2014. [Google Scholar] [CrossRef]
- Garofalo, M.; Villa, A.; Crescenti, D.; Marzagalli, M.; Kuryk, L.; Limonta, P.; Mazzaferro, V.; Ciana, P. Heterologous and cross-species tropism of cancer-derived extracellular vesicles. Theranostics 2019, 9, 5681–5693. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Cao, X. Organotropic metastasis: Role of tumor exosomes. Cell Res. 2015, 26, 149–150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, J.; Dong, Y.; Li, Y.; Li, W.; Cheng, K.; Qian, Y.; Xu, G.; Zhang, X.; Hu, L.; Chen, P.; et al. Designer Exosomes for Active Targeted Chemo-Photothermal Synergistic Tumor Therapy. Adv. Funct. Mater. 2018, 28, 1707360. [Google Scholar] [CrossRef]
- Huang, R.; Rofstad, E.K. Integrins as therapeutic targets in the organ-specific metastasis of human malignant melanoma. J. Exp. Clin. Cancer Res. 2018, 37, 1–14. [Google Scholar] [CrossRef]
- Rana, S.; Yue, S.; Stadel, D.; Zöller, M. Toward tailored exosomes: The exosomal tetraspanin web contributes to target cell selection. Int. J. Biochem. Cell Biol. 2012, 44, 1574–1584. [Google Scholar] [CrossRef] [PubMed]
- Rodrigues, G.; Hoshino, A.; Kenific, C.M.; Matei, I.R.; Steiner, L.; Freitas, D.; Kim, H.S.; Oxley, P.R.; Scandariato, I.; Casanova-Salas, I.; et al. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat. Cell Biol. 2019, 21, 1403–1412. [Google Scholar] [CrossRef]
- Franzen, C.A.; Simms, P.E.; Van Huis, A.F.; Foreman, K.E.; Kuo, P.C.; Gupta, G.N. Characterization of Uptake and Internalization of Exosomes by Bladder Cancer Cells. BioMed Res. Int. 2014, 2014, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Escrevente, C.; Keller, S.; Altevogt, P.; Costa, J. Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer 2011, 11, 108. [Google Scholar] [CrossRef] [Green Version]
- Matsumoto, A.; Takahashi, Y.; Nishikawa, M.; Sano, K.; Morishita, M.; Charoenviriyakul, C.; Saji, H.; Takakura, Y. Accelerated growth of B16 BL 6 tumor in mice through efficient uptake of their own exosomes by B16 BL 6 cells. Cancer Sci. 2017, 108, 1803–1810. [Google Scholar] [CrossRef] [PubMed]
- Kim, M.S.; Haney, M.J.; Zhao, Y.; Yuan, D.; Deygen, I.; Klyachko, N.L.; Kabanov, A.V.; Batrakova, E.V. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: In vitro and in vivo evaluations. Nanomedicine 2018, 14, 195–204. [Google Scholar] [CrossRef] [PubMed]
- Aspe, J.R.; Osterman, C.D.; Jutzy, J.M.; Deshields, S.; Whang, S.; Wall, N.R. Enhancement of Gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant. J. Extracell. Vesicles 2014, 3, 1–9. [Google Scholar] [CrossRef]
- Hood, J.L. Post isolation modification of exosomes for nanomedicine applications. Nanomedicine 2016, 11, 1745–1756. [Google Scholar] [CrossRef] [Green Version]
- Kooijmans, S.A.A.; Aleza, C.G.; Roffler, S.R.; Van Solinge, W.W.; Vader, P.; Schiffelers, R.M. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting. J. Extracell. Vesicles 2016, 5, 31053. [Google Scholar] [CrossRef] [PubMed]
- Kamerkar, S.; LeBleu, V.S.; Sugimoto, H.; Yang, S.; Ruivo, C.; Melo, S.; Lee, J.J.; Kalluri, R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nat. Cell Biol. 2017, 546, 498–503. [Google Scholar] [CrossRef]
- Limkin, E.J.; Sun, R.; Dercle, L.; Zacharaki, E.I.; Robert, C.; Reuzé, S.; Schernberg, A.; Paragios, N.; Deutsch, E.; Ferté, C. Promises and challenges for the implementation of computational medical imaging (radiomics) in oncology. Ann. Oncol. 2017, 28, 1191–1206. [Google Scholar] [CrossRef] [PubMed]
- Pegtel, D.M.; Cosmopoulos, K.; Thorley-Lawson, D.A.; van Eijndhoven, M.A.J.; Hopmans, E.S.; Lindenberg, J.L.; de Gruijl, T.D.; Würdinger, T.; Middeldorp, J. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. USA 2010, 107, 6328–6333. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tian, T.; Zhu, Y.-L.; Zhou, Y.-Y.; Liang, G.-F.; Wang, Y.-Y.; Hu, F.-H.; Xiao, Z.-D. Exosome Uptake through Clathrin-mediated Endocytosis and Macropinocytosis and Mediating miR-21 Delivery. J. Biol. Chem. 2014, 289, 22258–22267. [Google Scholar] [CrossRef] [Green Version]
- Lai, C.P.-K.; Kim, E.Y.; Badr, C.E.; Weissleder, R.; Mempel, T.R.; Tannous, B.A.; Breakefield, X.O. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat. Commun. 2015, 6, 7029. [Google Scholar] [CrossRef]
- Lai, C.P.-K.; Tannous, B.A.; Breakefield, X.O. Noninvasive in vivo monitoring of extracellular vesicles. In Breast Cancer; Springer Science and Business Media LLC: Berlin, Germany, 2013; Volume 1098, pp. 249–258. [Google Scholar]
- Gangadaran, P.; Li, X.J.; Kalimuthu, S.K.; Min, O.J.; Hong, C.M.; Rajendran, R.L.; Lee, H.W.; Zhu, L.; Baek, S.H.; Jeong, S.Y.; et al. New Optical Imaging Reporter-labeled Anaplastic Thyroid Cancer-Derived Extracellular Vesicles as a Platform for In Vivo Tumor Targeting in a Mouse Model. Sci. Rep. 2018, 8, 1–11. [Google Scholar] [CrossRef]
- Zong, S.; Zong, J.; Chen, C.; Jiang, X.; Zhang, Y.; Wang, Z.; Cui, Y. Single molecule localization imaging of exosomes using blinking silicon quantum dots. Nanotechnology 2017, 29, 065705. [Google Scholar] [CrossRef] [PubMed]
- Jiang, X.; Zong, S.; Chen, C.; Zhang, Y.; Wang, Z.; Cui, Y. Gold–carbon dots for the intracellular imaging of cancer-derived exosomes. Nanotechnology 2018, 29, 175701. [Google Scholar] [CrossRef] [PubMed]
- Jung, K.O.; Jo, H.; Yu, J.H.; Gambhir, S.S.; Pratx, G. Development and MPI tracking of novel hypoxia-targeted theranostic exosomes. Biomaterials 2018, 177, 139–148. [Google Scholar] [CrossRef]
- Hu, L.; Wickline, S.A.; Hood, J.L. Magnetic resonance imaging of melanoma exosomes in lymph nodes. Magn. Reson. Med. 2015, 74, 266–271. [Google Scholar] [CrossRef]
- Singh, P.; Pandit, S.; Mokkapati, V.R.S.S.; Garg, A.; Ravikumar, V.; Mijakovic, I. Gold Nanoparticles in Diagnostics and Therapeutics for Human Cancer. Int. J. Mol. Sci. 2018, 19, 1979. [Google Scholar] [CrossRef] [PubMed]
- Menon, J.; Jadeja, P.; Tambe, P.; Vu, K.; Yuan, B.; Nguyen, K.T. Nanomaterials for Photo-Based Diagnostic and Therapeutic Applications. Theranostics 2013, 3, 152–166. [Google Scholar] [CrossRef] [PubMed]
- Zhao, L.; Kim, T.-H.; Kim, H.-W.; Ahn, J.-C.; Kim, S.Y. Surface-enhanced Raman scattering (SERS)-active gold nanochains for multiplex detection and photodynamic therapy of cancer. Acta Biomater. 2015, 20, 155–164. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Wang, J.; Wientjes, M.G.; Au, J.L.-S. Delivery of nanomedicines to extracellular and intracellular compartments of a solid tumor. Adv. Drug Deliv. Rev. 2012, 64, 29–39. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kooijmans, S.A.A.; Schiffelers, R.M.; Zarovni, N.; Vago, R. Modulation of tissue tropism and biological activity of exosomes and other extracellular vesicles: New nanotools for cancer treatment. Pharmacol. Res. 2016, 111, 487–500. [Google Scholar] [CrossRef]
- Richardson, J.J.; Ejima, H. Surface Engineering of Extracellular Vesicles through Chemical and Biological Strategies. Chem. Mater. 2019, 31, 2191–2201. [Google Scholar] [CrossRef]
- Choi, D.-S.; Kim, D.-K.; Kim, Y.-K.; Gho, Y.S. Proteomics of extracellular vesicles: Exosomes and ectosomes. Mass Spectrom. Rev. 2015, 34, 474–490. [Google Scholar] [CrossRef]
- Meng, W.; He, C.; Hao, Y.; Wang, L.; Li, L.; Zhu, G. Prospects and challenges of extracellular vesicle-based drug delivery system: Considering cell source. Drug Deliv. 2020, 27, 585–598. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jia, G.; Han, Y.; An, Y.; Ding, Y.; He, C.; Wang, X.; Tang, Q. NRP-1 targeted and cargo-loaded exosomes facilitate simultaneous imaging and therapy of glioma in vitro and in vivo. Biomaterials 2018, 178, 302–316. [Google Scholar] [CrossRef]
- Silva, J.; Garcia, V.; Rodriguez, M.; Compte, M.; Cisneros, E.; Veguillas, P.; Garcia, J.M.; Dominguez, G.; Campos-Martin, Y.; Cuevas, J.; et al. Analysis of exosome release and its prognostic value in human colorectal cancer. Genes Chromosom. Cancer 2012, 51, 409–418. [Google Scholar] [CrossRef] [PubMed]
- Yamashita, T.; Kamada, H.; Kanasaki, S.; Maeda, Y.; Nagano, K.; Abe, Y.; Yoshioka, Y.; Tsutsumi, Y.; Katayama, S.; Inoue, M.; et al. Epidermal growth factor receptor localized to exosome membranes as a possible biomarker for lung cancer diagnosis. Die Pharm. 2013, 68, 969–973. [Google Scholar]
- Georgantzoglou, N.; Pergaris, A.; Masaoutis, C.; Theocharis, S. Extracellular Vesicles as Biomarkers Carriers in Bladder Cancer: Diagnosis, Surveillance, and Treatment. Int. J. Mol. Sci. 2021, 22, 2744. [Google Scholar] [CrossRef]
- Li, Z.; Jiang, P.; Li, J.; Peng, M.; Zhao, X.; Zhang, X.; Chen, K.; Zhang, Y.; Liu, H.; Gan, L.; et al. Tumor-derived exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA in pancreatic ductal adenocarcinoma. Oncogene 2018, 37, 3822–3838. [Google Scholar] [CrossRef]
- Huang, X.; Yuan, T.; Liang, M.; Du, M.; Xia, S.; Dittmar, R.; Wang, D.; See, W.; Costello, B.A.; Quevedo, F.; et al. Exosomal miR-1290 and miR-375 as Prognostic Markers in Castration-resistant Prostate Cancer. Eur. Urol. 2015, 67, 33–41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Buscail, E.; Alix-Panabières, C.; Quincy, P.; Cauvin, T.; Chauvet, A.; Degrandi, O.; Caumont, C.; Verdon, S.; Lamrissi, I.; Moranvillier, I.; et al. High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery. Cancers 2019, 11, 1656. [Google Scholar] [CrossRef] [Green Version]
- Takahasi, K.; Iinuma, H.; Wada, K.; Minezaki, S.; Kawamura, S.; Kainuma, M.; Ikeda, Y.; Shibuya, M.; Miura, F.; Sano, K. Usefulness of exosome-encapsulated microRNA-451a as a minimally invasive biomarker for prediction of recurrence and prognosis in pancreatic ductal adenocarcinoma. J. Hepato Biliary Pancreat. Sci. 2017, 25, 155–161. [Google Scholar] [CrossRef]
- Kawamura, S.; Iinuma, H.; Wada, K.; Takahashi, K.; Minezaki, S.; Kainuma, M.; Shibuya, M.; Miura, F.; Sano, K. Exosome-encapsulated microRNA-4525, microRNA-451a and microRNA-21 in portal vein blood is a high-sensitive liquid biomarker for the selection of high-risk pancreatic ductal adenocarcinoma patients. J. Hepato Biliary Pancreat. Sci. 2019, 26, 63–72. [Google Scholar] [CrossRef]
- ClinicalTrials.gov. 2021. Available online: https://clinicaltrials.gov/ct2/results?term=Exosomes+cancer&age_v=&gndr=&type=&rslt=&Search=Apply (accessed on 3 June 2021).
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Burgos-Ravanal, R.; Campos, A.; Díaz-Vesga, M.C.; González, M.F.; León, D.; Lobos-González, L.; Leyton, L.; Kogan, M.J.; Quest, A.F.G. Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications. Cancers 2021, 13, 3324. https://doi.org/10.3390/cancers13133324
Burgos-Ravanal R, Campos A, Díaz-Vesga MC, González MF, León D, Lobos-González L, Leyton L, Kogan MJ, Quest AFG. Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications. Cancers. 2021; 13(13):3324. https://doi.org/10.3390/cancers13133324
Chicago/Turabian StyleBurgos-Ravanal, Renato, América Campos, Magda C. Díaz-Vesga, María Fernanda González, Daniela León, Lorena Lobos-González, Lisette Leyton, Marcelo J. Kogan, and Andrew F. G. Quest. 2021. "Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications" Cancers 13, no. 13: 3324. https://doi.org/10.3390/cancers13133324