Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC)
Abstract
1. Introduction
2. Intercellular Communication by Exosomes
3. Exosomes in Cancer
4. Diagnostic Application of Exosomes
4.1. Exosomal Blood Levels Correlate With Clinical Disease
4.2. Isolation of Exosomes
4.3. Advantages and Drawbacks of Exosomal Applications
4.4. Exosome Tropism and Building of a Premetastatic Niche
4.5. Exosomal Alterations with Active Therapy
5. Therapeutic Approaches Based On Exosomes
5.1. Modulation Of Immune System
5.2. Loaded Exosomes as Targeted Drug Delivery
5.3. Modified Exosomes as Vaccinations
5.4. Engineered/Designer Exosomes
5.5. Exosomes in Immune-Modulatory Therapies
5.6. Blocking/Elimination of Exosomes
5.7. Challenges to Overcome Application of Exosomes
6. Ongoing Clinical Trials with Exosomes in Cancer
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [PubMed]
- Harding, C.; Heuser, J.; Stahl, P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 1983, 97, 329–339. [Google Scholar] [CrossRef] [PubMed]
- Raposo, G.; Nijman, H.W.; Stoorvogel, W.; Liejendekker, R.; Harding, C.V.; Melief, C.J.; Geuze, H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 1996, 183, 1161–1172. [Google Scholar] [CrossRef] [PubMed]
- Mathieu, M.; Martin-Jaular, L.; Lavieu, G.; Thery, C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat. Cell Biol. 2019, 21, 9–17. [Google Scholar] [CrossRef]
- Keller, S.; Ridinger, J.; Rupp, A.K.; Janssen, J.W.; Altevogt, P. Body fluid derived exosomes as a novel template for clinical diagnostics. J. Transl. Med. 2011, 9, 86. [Google Scholar] [CrossRef]
- Colombo, M.; Moita, C.; van Niel, G.; Kowal, J.; Vigneron, J.; Benaroch, P.; Manel, N.; Moita, L.F.; Thery, C.; Raposo, G. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 2013, 126, 5553–5565. [Google Scholar] [CrossRef]
- TEOE, B. Battle of Marathon. In Encylopaedia Britannica; Encyclopaedia Britannica Inc.: Chicago, IL, USA, 1998. [Google Scholar]
- Xin, T.; Greco, V.; Myung, P. Hardwiring stem cell communication through tissue structure. Cell 2016, 164, 1212–1225. [Google Scholar] [CrossRef]
- Thakur, B.K.; Zhang, H.; Becker, A.; Matei, I.; Huang, Y.; Costa-Silva, B.; Zheng, Y.; Hoshino, A.; Brazier, H.; Xiang, J.; et al. Double-stranded DNA in exosomes: A novel biomarker in cancer detection. Cell Res. 2014, 24, 766–769. [Google Scholar] [CrossRef]
- Muller, L.; Mitsuhashi, M.; Simms, P.; Gooding, W.E.; Whiteside, T.L. Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets. Sci. Rep. 2016, 6, 20254. [Google Scholar] [CrossRef]
- Muller, L.; Simms, P.; Hong, C.S.; Nishimura, M.I.; Jackson, E.K.; Watkins, S.C.; Whiteside, T.L. Human tumor-derived exosomes (TEX) regulate Treg functions via cell surface signaling rather than uptake mechanisms. Oncoimmunology 2017, 6, e1261243. [Google Scholar] [CrossRef]
- Adamczyk, K.A.; Klein-Scory, S.; Tehrani, M.M.; Warnken, U.; Schmiegel, W.; Schnolzer, M.; Schwarte-Waldhoff, I. Characterization of soluble and exosomal forms of the EGFR released from pancreatic cancer cells. Life Sci. 2011, 89, 304–312. [Google Scholar] [CrossRef] [PubMed]
- Bloomston, M.; Bhardwaj, A.; Ellison, E.C.; Frankel, W.L. Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig. Surg. 2006, 23, 74–79. [Google Scholar] [CrossRef] [PubMed]
- Nuzhat, Z.; Kinhal, V.; Sharma, S.; Rice, G.E.; Joshi, V.; Salomon, C. Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression. Oncotarget 2017, 8, 17279–17291. [Google Scholar] [CrossRef] [PubMed]
- Melo, S.A.; Luecke, L.B.; Kahlert, C.; Fernandez, A.F.; Gammon, S.T.; Kaye, J.; LeBleu, V.S.; Mittendorf, E.A.; Weitz, J.; Rahbari, N.; et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 2015, 523, 177–182. [Google Scholar] [CrossRef]
- Kahlert, C.; Melo, S.A.; Protopopov, A.; Tang, J.; Seth, S.; Koch, M.; Zhang, J.; Weitz, J.; Chin, L.; Futreal, A.; et al. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J. Biol. Chem. 2014, 289, 3869–3875. [Google Scholar] [CrossRef]
- Dreyer, F.; Baur, A. Biogenesis and Functions of Exosomes and Extracellular Vesicles. Methods Mol. Biol. 2016, 1448, 201–216. [Google Scholar] [CrossRef]
- Andre, F.; Schartz, N.E.; Movassagh, M.; Flament, C.; Pautier, P.; Morice, P.; Pomel, C.; Lhomme, C.; Escudier, B.; Le Chevalier, T.; et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet 2002, 360, 295–305. [Google Scholar] [CrossRef]
- Tetta, C.; Ghigo, E.; Silengo, L.; Deregibus, M.C.; Camussi, G. Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine 2013, 44, 11–19. [Google Scholar] [CrossRef]
- Joyce, D.P.; Kerin, M.J.; Dwyer, R.M. Exosome-encapsulated microRNAs as circulating biomarkers for breast cancer. Int. J. Cancer 2016, 139, 1443–1448. [Google Scholar] [CrossRef]
- Jia, Y.; Chen, Y.; Wang, Q.; Jayasinghe, U.; Luo, X.; Wei, Q.; Wang, J.; Xiong, H.; Chen, C.; Xu, B.; et al. Exosome: Emerging biomarker in breast cancer. Oncotarget 2017, 8, 41717–41733. [Google Scholar] [CrossRef]
- Sandfeld-Paulsen, B.; Jakobsen, K.R.; Baek, R.; Folkersen, B.H.; Rasmussen, T.R.; Meldgaard, P.; Varming, K.; Jorgensen, M.M.; Sorensen, B.S. Exosomal proteins as diagnostic biomarkers in lung cancer. J. Thorac. Oncol. 2016, 11, 1701–1710. [Google Scholar] [CrossRef] [PubMed]
- Dejima, H.; Iinuma, H.; Kanaoka, R.; Matsutani, N.; Kawamura, M. Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer. Oncol. Lett. 2017, 13, 1256–1263. [Google Scholar] [CrossRef]
- Alipoor, S.D.; Adcock, I.M.; Garssen, J.; Mortaz, E.; Varahram, M.; Mirsaeidi, M.; Velayati, A. The roles of miRNAs as potential biomarkers in lung diseases. Eur. J. Pharmacol. 2016, 791, 395–404. [Google Scholar] [CrossRef] [PubMed]
- Reclusa, P.; Sirera, R.; Araujo, A.; Giallombardo, M.; Valentino, A.; Sorber, L.; Bazo, I.G.; Pauwels, P.; Rolfo, C. Exosomes genetic cargo in lung cancer: A truly Pandora’s box. Transl. Lung Cancer Res. 2016, 5, 483–491. [Google Scholar] [CrossRef] [PubMed]
- Ueda, K.; Ishikawa, N.; Tatsuguchi, A.; Saichi, N.; Fujii, R.; Nakagawa, H. Antibody-coupled monolithic silica microtips for highthroughput molecular profiling of circulating exosomes. Sci. Rep. 2014, 4, 6232. [Google Scholar] [CrossRef] [PubMed]
- Jakobsen, K.R.; Paulsen, B.S.; Baek, R.; Varming, K.; Sorensen, B.S.; Jorgensen, M.M. Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma. J. Extracell. Vesicles 2015, 4, 26659. [Google Scholar] [CrossRef] [PubMed]
- Redzic, J.S.; Ung, T.H.; Graner, M.W. Glioblastoma extracellular vesicles: Reservoirs of potential biomarkers. Pharmgenomics Pers. Med. 2014, 7, 65–77. [Google Scholar] [CrossRef]
- Muller, L.; Muller-Haegele, S.; Mitsuhashi, M.; Gooding, W.; Okada, H.; Whiteside, T.L. Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival. Oncoimmunology 2015, 4, e1008347. [Google Scholar] [CrossRef]
- 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, corrected in Nat. Med. 2016, 22, 1502, doi:10.1038/nm1216-1502b. [Google Scholar] [CrossRef]
- Rashid, M.H.; Borin, T.F.; Ara, R.; Angara, K.; Cai, J.; Achyut, B.R.; Liu, Y.; Arbab, A.S. Differential in vivo biodistribution of (131)I-labeled exosomes from diverse cellular origins and its implication for theranostic application. Nanomedicine 2019, 21, 102072. [Google Scholar] [CrossRef]
- Skog, J.; Wurdinger, T.; van Rijn, S.; Meijer, D.H.; Gainche, L.; Sena-Esteves, M.; 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]
- Garcia-Silva, S.; Benito-Martin, A.; Sanchez-Redondo, S.; Hernandez-Barranco, A.; Ximenez-Embun, P.; Nogues, L.; Mazariegos, M.S.; Brinkmann, K.; Amor Lopez, A.; Meyer, L.; et al. Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAF (V600E) mutation. J. Exp. Med. 2019, 216, 1061–1070. [Google Scholar] [CrossRef] [PubMed]
- Muller, L.; Hong, C.S.; Stolz, D.B.; Watkins, S.C.; Whiteside, T.L. Isolation of biologically-active exosomes from human plasma. J. Immunol. Methods 2014, 411, 55–65. [Google Scholar] [CrossRef] [PubMed]
- Theodoraki, M.N.; Hoffmann, T.K.; Jackson, E.K.; Whiteside, T.L. Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competence. Clin. Exp. Immunol. 2018, 194, 67–78. [Google Scholar] [CrossRef]
- Ludwig, S.; Floros, T.; Theodoraki, M.N.; Hong, C.S.; Jackson, E.K.; Lang, S.; Whiteside, T.L. Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease Activity in Patients with Head and Neck Cancer. Clin. Cancer Res. 2017, 23, 4843–4854. [Google Scholar] [CrossRef] [PubMed]
- Isola, A.L.; Chen, S. Exosomes: The Messengers of Health and Disease. Curr. Neuropharmacol. 2017, 15, 157–165. [Google Scholar] [CrossRef]
- Whiteside, T.L. Tumor-Derived Exosomes and Their Role in Cancer Progression. Adv. Clin. Chem. 2016, 74, 103–141. [Google Scholar] [CrossRef]
- Theodoraki, M.N.; Hoffmann, T.K.; Whiteside, T.L. Separation of plasma-derived exosomes into CD3((+)) and CD3((-)) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patients. Clin. Exp. Immunol. 2018, 192, 271–283. [Google Scholar] [CrossRef]
- Hong, C.S.; Funk, S.; Whiteside, T.L. Isolation of Biologically Active Exosomes from Plasma of Patients with Cancer. Methods Mol. Biol. 2017, 1633, 257–265. [Google Scholar] [CrossRef]
- Nonaka, T.; Wong, D.T.W. Liquid Biopsy in Head and Neck Cancer: Promises and Challenges. J. Dent. Res. 2018, 97, 701–708. [Google Scholar] [CrossRef]
- Whiteside, T.L. Extracellular vesicles isolation and their biomarker potential: Are we ready for testing? Ann. Transl. Med. 2017, 5, 54. [Google Scholar] [CrossRef] [PubMed]
- Thery, C.; Amigorena, S.; Raposo, G.; Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. 2006, 3, 3.22.1–3.22.29. [Google Scholar] [CrossRef] [PubMed]
- Taylor, D.D.; Shah, S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods 2015, 87, 3–10. [Google Scholar] [CrossRef]
- Van Deun, J.; Mestdagh, P.; Sormunen, R.; Cocquyt, V.; Vermaelen, K.; Vandesompele, J.; Bracke, M.; De Wever, O.; Hendrix, A. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J. Extracell. Vesicles 2014, 3. [Google Scholar] [CrossRef] [PubMed]
- Lasser, C.; Thery, C.; Buzas, E.I.; Mathivanan, S.; Zhao, W.; Gho, Y.S.; Lotvall, J. The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles. J. Extracell. Vesicles 2016, 5, 34299. [Google Scholar] [CrossRef] [PubMed]
- Witwer, K.W.; Buzas, E.I.; Bemis, L.T.; Bora, A.; Lasser, C.; Lotvall, J.; Nolte-’t Hoen, E.N.; Piper, M.G.; Sivaraman, S.; Skog, J.; et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell. Vesicles 2013, 2. [Google Scholar] [CrossRef] [PubMed]
- Hong, C.S.; Danet-Desnoyers, G.; Shan, X.; Sharma, P.; Whiteside, T.L.; Boyiadzis, M. Human acute myeloid leukemia blast-derived exosomes in patient-derived xenograft mice mediate immune suppression. Exp. Hematol. 2019, 76, 60–66.e2. [Google Scholar] [CrossRef] [PubMed]
- 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, 14684. [Google Scholar] [CrossRef] [PubMed]
- Jia, S.; Zhang, R.; Li, Z.; Li, J. Clinical and biological significance of circulating tumor cells, circulating tumor DNA, and exosomes as biomarkers in colorectal cancer. Oncotarget 2017, 8, 55632–55645. [Google Scholar] [CrossRef] [PubMed]
- Alimirzaie, S.; Bagherzadeh, M.; Akbari, M.R. Liquid biopsy in breast cancer: A comprehensive review. Clin. Genet. 2019, 95, 643–660. [Google Scholar] [CrossRef]
- Scholer, L.V.; Reinert, T.; Orntoft, M.W.; Kassentoft, C.G.; Arnadottir, S.S.; Vang, S.; Nordentoft, I.; Knudsen, M.; Lamy, P.; Andreasen, D.; et al. Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer. Clin. Cancer Res. 2017, 23, 5437–5445. [Google Scholar] [CrossRef]
- Hoshino, A.; Costa-Silva, B.; Shen, T.L.; Rodrigues, G.; Hashimoto, A.; Tesic Mark, M.; 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]
- 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]
- Rodriguez Zorrilla, S.; Perez-Sayans, M.; Fais, S.; Logozzi, M.; Gallas Torreira, M.; Garcia Garcia, A. A Pilot Clinical Study on the Prognostic Relevance of Plasmatic Exosomes Levels in Oral Squamous Cell Carcinoma Patients. Cancers 2019, 11, 429. [Google Scholar] [CrossRef] [PubMed]
- Knowles, J.A.; Golden, B.; Yan, L.; Carroll, W.R.; Helman, E.E.; Rosenthal, E.L. Disruption of the AKT pathway inhibits metastasis in an orthotopic model of head and neck squamous cell carcinoma. Laryngoscope 2011, 121, 2359–2365. [Google Scholar] [CrossRef] [PubMed]
- Bussink, J.; van der Kogel, A.J.; Kaanders, J.H. Activation of the PI3-K/AKT pathway and implications for radioresistance mechanisms in head and neck cancer. Lancet Oncol. 2008, 9, 288–296. [Google Scholar] [CrossRef]
- Liu, Q.; Turner, K.M.; Alfred Yung, W.K.; Chen, K.; Zhang, W. Role of AKT signaling in DNA repair and clinical response to cancer therapy. Neuro Oncol. 2014, 16, 1313–1323. [Google Scholar] [CrossRef]
- Mutschelknaus, L.; Azimzadeh, O.; Heider, T.; Winkler, K.; Vetter, M.; Kell, R.; Tapio, S.; Merl-Pham, J.; Huber, S.M.; Edalat, L.; et al. Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells. Sci. Rep. 2017, 7, 12423. [Google Scholar] [CrossRef]
- Landskron, G.; De la Fuente, M.; Thuwajit, P.; Thuwajit, C.; Hermoso, M.A. Chronic inflammation and cytokines in the tumor microenvironment. J. Immunol. Res. 2014, 2014, 149185. [Google Scholar] [CrossRef]
- Bermejo-Martin, J.F.; Martin-Loeches, I.; Bosinger, S. Inflammation and infection in critical care medicine. Mediators Inflamm. 2014, 2014, 456256. [Google Scholar] [CrossRef]
- Bretz, N.P.; Ridinger, J.; Rupp, A.K.; Rimbach, K.; Keller, S.; Rupp, C.; Marme, F.; Umansky, L.; Umansky, V.; Eigenbrod, T.; et al. Body fluid exosomes promote secretion of inflammatory cytokines in monocytic cells via Toll-like receptor signaling. J. Biol. Chem. 2013, 288, 36691–36702. [Google Scholar] [CrossRef] [PubMed]
- Karin, M.; Cao, Y.; Greten, F.R.; Li, Z.W. NF-kappaB in cancer: From innocent bystander to major culprit. Nat. Rev. Cancer 2002, 2, 301–310. [Google Scholar] [CrossRef] [PubMed]
- Bromberg, J.; Darnell, J.E., Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 2000, 19, 2468–2473. [Google Scholar] [CrossRef] [PubMed]
- Andreola, G.; Rivoltini, L.; Castelli, C.; Huber, V.; Perego, P.; Deho, P.; Squarcina, P.; Accornero, P.; Lozupone, F.; Lugini, L.; et al. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J. Exp. Med. 2002, 195, 1303–1316. [Google Scholar] [CrossRef]
- Taylor, D.D.; Gercel-Taylor, C. Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects. Br. J. Cancer 2005, 92, 305–311. [Google Scholar] [CrossRef] [PubMed]
- Huber, V.; Fais, S.; Iero, M.; Lugini, L.; Canese, P.; Squarcina, P.; Zaccheddu, A.; Colone, M.; Arancia, G.; Gentile, M.; et al. Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: Role in immune escape. Gastroenterology 2005, 128, 1796–1804. [Google Scholar] [CrossRef]
- Clayton, A.; Mason, M.D. Exosomes in tumour immunity. Curr. Oncol. 2009, 16, 46–49. [Google Scholar] [CrossRef]
- Clayton, A.; Mitchell, J.P.; Court, J.; Mason, M.D.; Tabi, Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res. 2007, 67, 7458–7466. [Google Scholar] [CrossRef]
- Yokoi, A.; Yoshioka, Y.; Yamamoto, Y.; Ishikawa, M.; Ikeda, S.I.; Kato, T.; Kiyono, T.; Takeshita, F.; Kajiyama, H.; Kikkawa, F.; et al. Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer. Nat. Commun. 2017, 8, 14470. [Google Scholar] [CrossRef]
- Baj-Krzyworzeka, M.; Majka, M.; Pratico, D.; Ratajczak, J.; Vilaire, G.; Kijowski, J.; Reca, R.; Janowska-Wieczorek, A.; Ratajczak, M.Z. Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Exp. Hematol. 2002, 30, 450–459. [Google Scholar] [CrossRef]
- Sprague, D.L.; Elzey, B.D.; Crist, S.A.; Waldschmidt, T.J.; Jensen, R.J.; Ratliff, T.L. Platelet-mediated modulation of adaptive immunity: Unique delivery of CD154 signal by platelet-derived membrane vesicles. Blood 2008, 111, 5028–5036. [Google Scholar] [CrossRef] [PubMed]
- Folkman, J. Anti-angiogenesis: New concept for therapy of solid tumors. Ann. Surg. 1972, 175, 409–416. [Google Scholar] [CrossRef] [PubMed]
- Svensson, K.J.; Kucharzewska, P.; Christianson, H.C.; Skold, S.; Lofstedt, T.; Johansson, M.C.; Morgelin, M.; Bengzon, J.; Ruf, W.; Belting, M. Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. Proc. Natl. Acad. Sci. USA 2011, 108, 13147–13152. [Google Scholar] [CrossRef] [PubMed]
- Hong, B.S.; Cho, J.H.; Kim, H.; Choi, E.J.; Rho, S.; Kim, J.; Kim, J.H.; Choi, D.S.; Kim, Y.K.; Hwang, D.; et al. Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genom. 2009, 10, 556. [Google Scholar] [CrossRef]
- Grange, C.; Tapparo, M.; Collino, F.; Vitillo, L.; Damasco, C.; Deregibus, M.C.; Tetta, C.; Bussolati, B.; Camussi, G. Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res. 2011, 71, 5346–5356. [Google Scholar] [CrossRef]
- Kosaka, N.; Iguchi, H.; Hagiwara, K.; Yoshioka, Y.; Takeshita, F.; Ochiya, T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J. Biol. Chem. 2013, 288, 10849–10859. [Google Scholar] [CrossRef]
- Li, R.; Wang, Y.; Zhang, X.; Feng, M.; Ma, J.; Li, J.; Yang, X.; Fang, F.; Xia, Q.; Zhang, Z.; et al. Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis. Mol. Cancer 2019, 18, 18. [Google Scholar] [CrossRef]
- Soldevilla, B.; Rodriguez, M.; San Millan, C.; Garcia, V.; Fernandez-Perianez, R.; Gil-Calderon, B.; Martin, P.; Garcia-Grande, A.; Silva, J.; Bonilla, F.; et al. Tumor-derived exosomes are enriched in DeltaNp73, which promotes oncogenic potential in acceptor cells and correlates with patient survival. Hum. Mol. Genet. 2014, 23, 467–478. [Google Scholar] [CrossRef]
- McCready, J.; Sims, J.D.; Chan, D.; Jay, D.G. Secretion of extracellular hsp90alpha via exosomes increases cancer cell motility: A role for plasminogen activation. BMC Cancer 2010, 10, 294. [Google Scholar] [CrossRef]
- Kim, J.W.; Wieckowski, E.; Taylor, D.D.; Reichert, T.E.; Watkins, S.; Whiteside, T.L. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin. Cancer Res. 2005, 11, 1010–1020. [Google Scholar]
- Czystowska, M.; Han, J.; Szczepanski, M.J.; Szajnik, M.; Quadrini, K.; Brandwein, H.; Hadden, J.W.; Signorelli, K.; Whiteside, T.L. IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death. Cell Death Differ. 2009, 16, 708–718. [Google Scholar] [CrossRef] [PubMed]
- Wieckowski, E.U.; Visus, C.; Szajnik, M.; Szczepanski, M.J.; Storkus, W.J.; 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] [PubMed]
- Fanini, F.; Fabbri, M. Cancer-derived exosomic microRNAs shape the immune system within the tumor microenvironment: State of the art. Semin. Cell Dev. Biol. 2017, 67, 23–28. [Google Scholar] [CrossRef]
- Zhang, H.G.; Grizzle, W.E. Exosomes: A novel pathway of local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions. Am. J. Pathol. 2014, 184, 28–41. [Google Scholar] [CrossRef] [PubMed]
- Whiteside, T.L. Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes). Biochem. Soc. Trans. 2013, 41, 245–251. [Google Scholar] [CrossRef] [PubMed]
- 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]
- Wiklander, O.P.; Nordin, J.Z.; O’Loughlin, A.; Gustafsson, Y.; Corso, G.; Mager, 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]
- Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29, 341–345. [Google Scholar] [CrossRef]
- Kim, M.S.; Haney, M.J.; Zhao, Y.; Mahajan, V.; Deygen, I.; Klyachko, N.L.; Inskoe, E.; Piroyan, A.; Sokolsky, M.; Okolie, O.; et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 2016, 12, 655–664. [Google Scholar] [CrossRef]
- Zhuang, X.; Xiang, X.; Grizzle, W.; Sun, D.; Zhang, S.; Axtell, R.C.; Ju, S.; Mu, J.; Zhang, L.; Steinman, L.; et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol. Ther. 2011, 19, 1769–1779. [Google Scholar] [CrossRef]
- Cooper, J.M.; Wiklander, P.B.; Nordin, J.Z.; Al-Shawi, R.; Wood, M.J.; Vithlani, M.; Schapira, A.H.; Simons, J.P.; El-Andaloussi, S.; Alvarez-Erviti, L. Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. Mov. Disord. 2014, 29, 1476–1485. [Google Scholar] [CrossRef] [PubMed]
- Wahlgren, J.; De, L.K.T.; Brisslert, M.; Vaziri Sani, F.; Telemo, E.; Sunnerhagen, P.; Valadi, H. Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res. 2012, 40, e130. [Google Scholar] [CrossRef]
- Ohno, S.; Takanashi, M.; Sudo, K.; Ueda, S.; Ishikawa, A.; Matsuyama, N.; Fujita, K.; Mizutani, T.; Ohgi, T.; Ochiya, T.; et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther. 2013, 21, 185–191. [Google Scholar] [CrossRef] [PubMed]
- Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Takeshita, F.; Matsuki, Y.; Ochiya, T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 2010, 285, 17442–17452. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Y.; Xiong, M.; Fang, L.; Jiang, L.; Wen, P.; Dai, C.; Zhang, C.Y.; Yang, J. miR-21-containing microvesicles from injured tubular epithelial cells promote tubular phenotype transition by targeting PTEN protein. Am. J. Pathol. 2013, 183, 1183–1196. [Google Scholar] [CrossRef]
- Zhang, Y.; Liu, D.; Chen, X.; Li, J.; Li, L.; Bian, Z.; Sun, F.; Lu, J.; Yin, Y.; Cai, X.; et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell 2010, 39, 133–144. [Google Scholar] [CrossRef]
- Zhang, Y.; Li, L.; Yu, J.; Zhu, D.; Zhang, Y.; Li, X.; Gu, H.; Zhang, C.Y.; Zen, K. Microvesicle-mediated delivery of transforming growth factor beta1 siRNA for the suppression of tumor growth in mice. Biomaterials 2014, 35, 4390–4400. [Google Scholar] [CrossRef]
- Zitvogel, L.; Regnault, A.; Lozier, A.; Wolfers, J.; Flament, C.; Tenza, D.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S. Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes. Nat. Med. 1998, 4, 594–600. [Google Scholar] [CrossRef]
- Dai, S.; Wei, D.; Wu, Z.; Zhou, X.; Wei, X.; Huang, H.; Li, G. Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol. Ther. 2008, 16, 782–790. [Google Scholar] [CrossRef]
- Kojima, R.; Bojar, D.; Rizzi, G.; Hamri, G.C.; El-Baba, M.D.; Saxena, P.; Auslander, S.; Tan, K.R.; Fussenegger, M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat. Commun. 2018, 9, 1305. [Google Scholar] [CrossRef]
- Topalian, S.L.; Drake, C.G.; Pardoll, D.M. Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell 2015, 27, 450–461. [Google Scholar] [CrossRef] [PubMed]
- Page, D.B.; Postow, M.A.; Callahan, M.K.; Allison, J.P.; Wolchok, J.D. Immune modulation in cancer with antibodies. Annu. Rev. Med. 2014, 65, 185–202. [Google Scholar] [CrossRef] [PubMed]
- Theodoraki, M.N.; Yerneni, S.S.; Hoffmann, T.K.; Gooding, W.E.; Whiteside, T.L. Clinical Significance of PD-L1(+) Exosomes in Plasma of Head and Neck Cancer Patients. Clin. Cancer Res. 2018, 24, 896–905. [Google Scholar] [CrossRef] [PubMed]
- 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]
- Zhang, J.; Gao, J.; Li, Y.; Nie, J.; Dai, L.; Hu, W.; Chen, X.; Han, J.; Ma, X.; Tian, G.; et al. Circulating PD-L1 in NSCLC patients and the correlation between the level of PD-L1 expression and the clinical characteristics. Thorac. Cancer 2015, 6, 534–538. [Google Scholar] [CrossRef]
- Okuma, Y.; Hosomi, Y.; Nakahara, Y.; Watanabe, K.; Sagawa, Y.; Homma, S. High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer. Lung Cancer 2017, 104, 1–6. [Google Scholar] [CrossRef]
- Poggio, M.; Hu, T.; Pai, C.C.; Chu, B.; Belair, C.D.; Chang, A.; Montabana, E.; Lang, U.E.; Fu, Q.; Fong, L.; et al. Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory. Cell 2019, 177, 414–427.e13. [Google Scholar] [CrossRef]
- Atai, N.A.; Balaj, L.; van Veen, H.; Breakefield, X.O.; Jarzyna, P.A.; Van Noorden, C.J.; Skog, J.; Maguire, C.A. Heparin blocks transfer of extracellular vesicles between donor and recipient cells. J. Neurooncol. 2013, 115, 343–351. [Google Scholar] [CrossRef]
- Balaj, L.; Atai, N.A.; Chen, W.; Mu, D.; Tannous, B.A.; Breakefield, X.O.; Skog, J.; Maguire, C.A. Heparin affinity purification of extracellular vesicles. Sci. Rep. 2015, 5, 10266. [Google Scholar] [CrossRef]
- Chapman, C.J.; Thorpe, A.J.; Murray, A.; Parsy-Kowalska, C.B.; Allen, J.; Stafford, K.M.; Chauhan, A.S.; Kite, T.A.; Maddison, P.; Robertson, J.F. Immunobiomarkers in small cell lung cancer: Potential early cancer signals. Clin. Cancer Res. 2011, 17, 1474–1480. [Google Scholar] [CrossRef]
- Zhong, L.; Coe, S.P.; Stromberg, A.J.; Khattar, N.H.; Jett, J.R.; Hirschowitz, E.A. Profiling tumor-associated antibodies for early detection of non-small cell lung cancer. J. Thorac. Oncol. 2006, 1, 513–519. [Google Scholar] [CrossRef] [PubMed]
- Li, G.; Miles, A.; Line, A.; Rees, R.C. Identification of tumour antigens by serological analysis of cDNA expression cloning. Cancer Immunol. Immunother. 2004, 53, 139–143. [Google Scholar] [CrossRef] [PubMed]
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Ebnoether, E.; Muller, L. Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC). Int. J. Mol. Sci. 2020, 21, 4344. https://doi.org/10.3390/ijms21124344
Ebnoether E, Muller L. Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC). International Journal of Molecular Sciences. 2020; 21(12):4344. https://doi.org/10.3390/ijms21124344
Chicago/Turabian StyleEbnoether, Eliane, and Laurent Muller. 2020. "Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC)" International Journal of Molecular Sciences 21, no. 12: 4344. https://doi.org/10.3390/ijms21124344
APA StyleEbnoether, E., & Muller, L. (2020). Diagnostic and Therapeutic Applications of Exosomes in Cancer with a Special Focus on Head and Neck Squamous Cell Carcinoma (HNSCC). International Journal of Molecular Sciences, 21(12), 4344. https://doi.org/10.3390/ijms21124344