Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space
Abstract
:1. Introduction
2. Results
2.1. Interferometric Analysis
2.1.1. Particle Concentration
2.1.2. Particle Size Distribution
2.2. Fluorescent Analysis
2.2.1. Total Fluorescent Particle Counts
2.2.2. Colocalization Analysis
Single Tetraspanin Surface Expression—CD9, CD63, and CD81
Co-expression of two Tetraspanins – CD9/CD63, CD9/CD81, and CD63/CD81
Co-Expression of all three Tetraspanins – CD9/CD63/CD81
3. Discussion
4. Materials and Methods
4.1. Cell Cultures
4.2. CellBox-1 Spaceflight Experiment
4.3. Exosome Harvest and Isolation
4.4. ExoView® Kit Assay Procedure
4.5. Digital Detection of Exosomes
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AB | Antibody |
EMT | Epithelial to Mesenchymal Transition |
EV | Extracellular Vesicle |
GM | Ground Module |
FM | Flight Module |
ILV | Intraluminal Vesicle |
MVBs | Multivesicular Bodies |
NTA | Nanoparticle Tracking Analysis |
ON | Overnight |
RPM | Random Positioning Machine |
RT | Room temperature |
SD | Standard Deviation |
SP-IRIS | Single Particle Interferometric Reflectance Imaging Sensor |
TME | Tumor Microenvironment |
References
- NASA. First Human-Made Object to Enter Space. Available online: https://www.nasa.gov/mission_pages/explorer/bumper.html (accessed on 7 August 2020).
- NASA. Space Programs. Available online: http://adc.gsfc.nasa.gov/adc/education/space_ex/probes.html (accessed on 2 July 2020).
- Mann, A. The Vostok Program: The Soviet’s First Crewed Spaceflight Program. Available online: https://www.space.com/vostok-program.html (accessed on 28 July 2020).
- SpaceX. Space Station—Transporting Humans to the Orbiting Laboratory. Available online: https://www.spacex.com/human-spaceflight/iss/index.html (accessed on 28 July 2020).
- Baldwin, K.M. Effect of spaceflight on the functional, biochemical, and metabolic properties of skeletal muscle. Med. Sci. Sports Exerc. 1996, 28, 983–987. [Google Scholar] [CrossRef]
- Baldwin, K.M.; White, T.P.; Arnaud, S.B.; Edgerton, V.R.; Kraemer, W.J.; Kram, R.; Raab-Cullen, D.; Snow, C.M. Musculoskeletal adaptations to weightlessness and development of effective countermeasures. Med. Sci. Sports Exerc. 1996, 28, 1247–1253. [Google Scholar] [CrossRef]
- Stampi, C. Sleep and circadian rhythms in space. J. Clin. Pharmacol. 1994, 34, 518–534. [Google Scholar] [CrossRef]
- Strollo, F. Hormonal changes in humans during spaceflight. Adv. Space Biol. Med. 1999, 7, 99–129. [Google Scholar] [CrossRef]
- Taylor, G.R. Overview of spaceflight immunology studies. J. Leukoc. Biol. 1993, 54, 179–188. [Google Scholar] [CrossRef] [PubMed]
- White, R.J.; Averner, M. Humans in space. Nature 2001, 409, 1115–1118. [Google Scholar] [CrossRef]
- White, R.J. Weightlessness and the human body. Sci. Am. 1998, 279, 58–63. [Google Scholar] [CrossRef] [PubMed]
- Garrett-Bakelman, F.E.; Darshi, M.; Green, S.J.; Gur, R.C.; Lin, L.; Macias, B.R.; McKenna, M.J.; Meydan, C.; Mishra, T.; Nasrini, J.; et al. The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight. Science 2019, 364. [Google Scholar] [CrossRef]
- Battista, N.; Meloni, M.A.; Bari, M.; Mastrangelo, N.; Galleri, G.; Rapino, C.; Dainese, E.; Agrò, A.F.; Pippia, P.; Maccarrone, M. 5-Lipoxygenase-dependent apoptosis of human lymphocytes in the International Space Station: Data from the ROALD experiment. FASEB J. 2012, 26, 1791–1798. [Google Scholar] [CrossRef] [PubMed]
- Herranz, R.; Anken, R.; Boonstra, J.; Braun, M.; Christianen, P.C.; de Geest, M.; Hauslage, J.; Hilbig, R.; Hill, R.J.; Lebert, M.; et al. Ground-based facilities for simulation of microgravity: Organism-specific recommendations for their use, and recommended terminology. Astrobiology 2013, 13, 1–17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hoson, T.; Kamisaka, S.; Masuda, Y.; Yamashita, M.; Buchen, B. Evaluation of the three-dimensional clinostat as a simulator of weightlessness. Planta 1997, 203 Suppl, S187–S197. [Google Scholar] [CrossRef]
- Pietsch, J.; Bauer, J.; Egli, M.; Infanger, M.; Wise, P.; Ulbrich, C.; Grimm, D. The effects of weightlessness on the human organism and mammalian cells. Curr. Mol. Med. 2011, 11, 350–364. [Google Scholar] [CrossRef]
- van Loon, J. Some history and use of the random positioning machine, RPM, in gravity related research. Adv. Space Res. 2007, 39, 1161–1165. [Google Scholar] [CrossRef]
- Maccarrone, M.; Battista, N.; Meloni, M.; Bari, M.; Galleri, G.; Pippia, P.; Cogoli, A.; Finazzi-Agrò, A. Creating conditions similar to those that occur during exposure of cells to microgravity induces apoptosis in human lymphocytes by 5-lipoxygenase-mediated mitochondrial uncoupling and cytochrome c release. J. Leukoc. Biol. 2003, 73, 472–481. [Google Scholar] [CrossRef]
- Schwarzenberg, M.; Pippia, P.; Meloni, M.A.; Cossu, G.; Cogoli-Greuter, M.; Cogoli, A. Signal transduction in T lymphocytes--a comparison of the data from space, the free fall machine and the random positioning machine. Adv. Space Res. 1999, 24, 793–800. [Google Scholar] [CrossRef]
- German Aerospace Center (DLR). Germany and China—Joint Experiments in Space. Available online: https://www.dlr.de/content/en/downloads/news-archive/2011/20111101_germany-and-china---joint-experiments-in-space_1805.pdf?__blob=publicationFile&v=10 (accessed on 1 November 2011).
- Kramer, C.D.; Kalla, E.M. The challenge of designing biomedical equipment during human research for long duration low-gravity NASA missions. In Proceedings of the 1997 16 Southern Biomedical Engineering Conference, Biloxi, MS, USA, 4–6 April 1997; pp. 30–37. [Google Scholar] [CrossRef]
- Pietsch, J.; Ma, X.; Wehland, M.; Aleshcheva, G.; Schwarzwälder, A.; Segerer, J.; Birlem, M.; Horn, A.; Bauer, J.; Infanger, M.; et al. Spheroid formation of human thyroid cancer cells in an automated culturing system during the Shenzhou-8 Space mission. Biomaterials 2013, 34, 7694–7705. [Google Scholar] [CrossRef]
- Riwaldt, S.; Pietsch, J.; Sickmann, A.; Bauer, J.; Braun, M.; Segerer, J.; Schwarzwälder, A.; Aleshcheva, G.; Corydon, T.J.; Infanger, M.; et al. Identification of proteins involved in inhibition of spheroid formation under microgravity. Proteomics 2015, 15, 2945–2952. [Google Scholar] [CrossRef] [PubMed]
- Riwaldt, S.; Bauer, J.; Pietsch, J.; Braun, M.; Segerer, J.; Schwarzwälder, A.; Corydon, T.J.; Infanger, M.; Grimm, D. The Importance of Caveolin-1 as Key-Regulator of Three-Dimensional Growth in Thyroid Cancer Cells Cultured under Real and Simulated Microgravity Conditions. Int. J. Mol. Sci. 2015, 16, 28296–28310. [Google Scholar] [CrossRef]
- Riwaldt, S.; Bauer, J.; Wehland, M.; Slumstrup, L.; Kopp, S.; Warnke, E.; Dittrich, A.; Magnusson, N.E.; Pietsch, J.; Corydon, T.J.; et al. Pathways Regulating Spheroid Formation of Human Follicular Thyroid Cancer Cells under Simulated Microgravity Conditions: A Genetic Approach. Int. J. Mol. Sci. 2016, 17, 528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Colombo, M.; Raposo, G.; Théry, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014, 30, 255–289. [Google Scholar] [CrossRef]
- Quek, C.; Hill, A.F. The role of extracellular vesicles in neurodegenerative diseases. Biochem. Biophys. Res. Commun. 2017, 483, 1178–1186. [Google Scholar] [CrossRef]
- Bank, I.E.; Timmers, L.; Gijsberts, C.M.; Zhang, Y.N.; Mosterd, A.; Wang, J.W.; Chan, M.Y.; De Hoog, V.; Lim, S.K.; Sze, S.K.; et al. The diagnostic and prognostic potential of plasma extracellular vesicles for cardiovascular disease. Expert Rev. Mol. Diagn. 2015, 15, 1577–1588. [Google Scholar] [CrossRef] [PubMed]
- 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]
- Orozco, A.F.; Lewis, D.E. Flow cytometric analysis of circulating microparticles in plasma. Cytometry A 2010, 77, 502–514. [Google Scholar] [CrossRef] [Green Version]
- Gonzales, P.A.; Pisitkun, T.; Hoffert, J.D.; Tchapyjnikov, D.; Star, R.A.; Kleta, R.; Wang, N.S.; Knepper, M.A. Large-scale proteomics and phosphoproteomics of urinary exosomes. J. Am. Soc. Nephrol. 2009, 20, 363–379. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sharma, S.; Gillespie, B.M.; Palanisamy, V.; Gimzewski, J.K. Quantitative nanostructural and single-molecule force spectroscopy biomolecular analysis of human-saliva-derived exosomes. Langmuir 2011, 27, 14394–14400. [Google Scholar] [CrossRef] [Green Version]
- Al-Nedawi, K.; Meehan, B.; Micallef, J.; Lhotak, V.; May, L.; Guha, A.; Rak, J. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 2008, 10, 619–624. [Google Scholar] [CrossRef]
- 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] [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] [PubMed]
- Skog, J.; Würdinger, T.; van Rijn, S.; Meijer, D.H.; Gainche, L.; Sena-Esteves, M.; Curry, W.T.; 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]
- Richards, K.E.; Zeleniak, A.E.; Fishel, M.L.; 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]
- Au Yeung, C.L.; Co, N.N.; Tsuruga, T.; Yeung, T.L.; Kwan, S.Y.; Leung, C.S.; Li, Y.; Lu, E.S.; Kwan, K.; Wong, K.K.; et al. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat. Commun. 2016, 7, 11150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leca, J.; Martinez, S.; Lac, S.; Nigri, J.; Secq, V.; Rubis, M.; Bressy, C.; Sergé, A.; Lavaut, M.N.; Dusetti, N.; et al. Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. J. Clin. Investig. 2016, 126, 4140–4156. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- 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]
- Whiteside, T.L. Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression. Vaccines 2016, 4, 35. [Google Scholar] [CrossRef] [PubMed]
- Peinado, H.; Alečković, M.; Lavotshkin, S.; Matei, I.; Costa-Silva, B.; Moreno-Bueno, G.; Hergueta-Redondo, M.; Williams, C.; García-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] [Green Version]
- Somasundaram, R.; Herlyn, M. Melanoma exosomes: Messengers of metastasis. Nat. Med. 2012, 18, 853–854. [Google Scholar] [CrossRef]
- Alderton, G.K. Metastasis. Exosomes drive premetastatic niche formation. Nat. Rev. Cancer 2012, 12, 447. [Google Scholar] [CrossRef]
- 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] [Green Version]
- Costa-Silva, B.; Aiello, N.M.; Ocean, A.J.; Singh, S.; Zhang, H.; Thakur, B.K.; Becker, A.; Hoshino, A.; Mark, M.T.; Molina, H.; et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 2015, 17, 816–826. [Google Scholar] [CrossRef]
- Nogués, L.; Benito-Martin, A.; Hergueta-Redondo, M.; Peinado, H. The influence of tumour-derived extracellular vesicles on local and distal metastatic dissemination. Mol. Aspects Med. 2018, 60, 15–26. [Google Scholar] [CrossRef] [PubMed]
- 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]
- 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]
- Hessvik, N.P.; Llorente, A. Current knowledge on exosome biogenesis and release. Cell Mol. Life Sci. 2018, 75, 193–208. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hartjes, T.A.; Mytnyk, S.; Jenster, G.W.; van Steijn, V.; van Royen, M.E. Extracellular Vesicle Quantification and Characterization: Common Methods and Emerging Approaches. Bioengineering 2019, 6, 7. [Google Scholar] [CrossRef] [Green Version]
- Filipe, V.; Hawe, A.; Jiskoot, W. Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res. 2010, 27, 796–810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Daaboul, G.G.; Gagni, P.; Benussi, L.; Bettotti, P.; Ciani, M.; Cretich, M.; Freedman, D.S.; Ghidoni, R.; Ozkumur, A.Y.; Piotto, C.; et al. Digital Detection of Exosomes by Interferometric Imaging. Sci. Rep. 2016, 6, 37246. [Google Scholar] [CrossRef]
- Lässer, C.; Eldh, M.; Lötvall, J. Isolation and characterization of RNA-containing exosomes. J. Vis. Exp. 2012, 59, e3037. [Google Scholar] [CrossRef] [PubMed]
- Avci, O.; Ünlü, N.L.; Özkumur, A.Y.; Ünlü, M.S. Interferometric Reflectance Imaging Sensor (IRIS)--A Platform Technology for Multiplexed Diagnostics and Digital Detection. Sensors 2015, 15, 17649–17665. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Harding, C.; Stahl, P. Transferrin recycling in reticulocytes: pH and iron are important determinants of ligand binding and processing. Biochem. Biophys. Res. Commun. 1983, 113, 650–658. [Google Scholar] [CrossRef]
- Pan, B.T.; Johnstone, R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell 1983, 33, 967–978. [Google Scholar] [CrossRef]
- Lane, R.E.; Korbie, D.; Trau, M.; Hill, M.M. Purification Protocols for Extracellular Vesicles. Methods Mol. Biol. 2017, 1660, 111–130. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gardiner, C.; Di Vizio, D.; Sahoo, S.; Théry, C.; Witwer, K.W.; Wauben, M.; Hill, A.F. Techniques used for the isolation and characterization of extracellular vesicles: Results of a worldwide survey. J. Extracell. Vesicles 2016, 5, 32945. [Google Scholar] [CrossRef] [PubMed]
- Shu, S.; Yang, Y.; Allen, C.L.; Hurley, E.; Tung, K.H.; Minderman, H.; Wu, Y.; Ernstoff, M.S. Purity and yield of melanoma exosomes are dependent on isolation method. J. Extracell. Vesicles 2020, 9, 1692401. [Google Scholar] [CrossRef] [Green Version]
- Brown, P.N.; Yin, H. Polymer-Based Purification of Extracellular Vesicles. Methods Mol. Biol. 2017, 1660, 91–103. [Google Scholar] [CrossRef]
- Lambrecht, G.; Petersen, N.; Weerts, G.; Pruett, C.; Evetts, S.; Stokes, M.; Hides, J. The role of physiotherapy in the European Space Agency strategy for preparation and reconditioning of astronauts before and after long duration space flight. Musculoskelet Sci. Pract. 2017, 27 Suppl 1, S15–S22. [Google Scholar] [CrossRef] [Green Version]
- Barratt, M.R.P.; Pool, S.L. (Eds.) Principles of Clinical Medicine for Space Flight, 1st ed.; Springer-Verlag: New York, NY, USA, 2008; p. 596. [Google Scholar] [CrossRef]
- Petersen, N.; Lambrecht, G.; Scott, J.; Hirsch, N.; Stokes, M.; Mester, J. Postflight reconditioning for European Astronauts—A case report of recovery after six months in space. Musculoskelet. Sci. Pract. 2017, 27 Suppl 1, S23–S31. [Google Scholar] [CrossRef] [Green Version]
- Claridge, B.; Kastaniegaard, K.; Stensballe, A.; Greening, D.W. Post-translational and transcriptional dynamics—regulating extracellular vesicle biology. Expert Rev. Proteom. 2019, 16, 17–31. [Google Scholar] [CrossRef]
- Challagundla, K.B.; Fanini, F.; Vannini, I.; Wise, P.; Murtadha, M.; Malinconico, L.; Cimmino, A.; Fabbri, M. microRNAs in the tumor microenvironment: Solving the riddle for a better diagnostics. Expert Rev. Mol. Diagn. 2014, 14, 565–574. [Google Scholar] [CrossRef]
- Challagundla, K.; Wise, P.; Fabbri, M. Exosomic microRNAs and Drug Resistance in the Neuroblastoma Environment. Poster Presentation. 2013. [Google Scholar]
- Barile, L.; Vassalli, G. Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol. Ther. 2017, 174, 63–78. [Google Scholar] [CrossRef] [Green Version]
- Grosse, J.; Wehland, M.; Pietsch, J.; Schulz, H.; Saar, K.; Hübner, N.; Eilles, C.; Bauer, J.; Abou-El-Ardat, K.; Baatout, S.; et al. Gravity-sensitive signaling drives 3-dimensional formation of multicellular thyroid cancer spheroids. FASEB J. 2012, 26, 5124–5140. [Google Scholar] [CrossRef] [Green Version]
- Ma, X.; Pietsch, J.; Wehland, M.; Schulz, H.; Saar, K.; Hübner, N.; Bauer, J.; Braun, M.; Schwarzwälder, A.; Segerer, J.; et al. Differential gene expression profile and altered cytokine secretion of thyroid cancer cells in space. FASEB J. 2014, 28, 813–835. [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] [PubMed] [Green Version]
- Murtadha, M.; Wise, P.; Neviani, P.; Challagundla, K.; Frediani, J.; Fabbri, M. TLR8 dependent economic miR0192 secreted by tumor associated macrophages (TAMs) modulates MYC and induces chemoresistance in neuroblastoma (NB). TSRI Poster Presentation. 2016. [Google Scholar]
- Andreu, Z.; Yáñez-Mó, M. Tetraspanins in extracellular vesicle formation and function. Front. Immunol. 2014, 5, 442. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- French, K.C.; Antonyak, M.A.; Cerione, R.A. Extracellular vesicle docking at the cellular port: Extracellular vesicle binding and uptake. Semin. Cell Dev. Biol. 2017, 67, 48–55. [Google Scholar] [CrossRef] [PubMed]
- Malla, R.R.; Pandrangi, S.; Kumari, S.; Gavara, M.M.; Badana, A.K. Exosomal tetraspanins as regulators of cancer progression and metastasis and novel diagnostic markers. Asia Pac. J. Clin. Oncol. 2018, 14, 383–391. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zöller, M. Tetraspanins: Push and pull in suppressing and promoting metastasis. Nat. Rev. Cancer 2009, 9, 40–55. [Google Scholar] [CrossRef]
- Reyes, R.; Cardeñes, B.; Machado-Pineda, Y.; Cabañas, C. Tetraspanin CD9: A Key Regulator of Cell Adhesion in the Immune System. Front. Immunol. 2018, 9, 863. [Google Scholar] [CrossRef] [PubMed]
- Scheller, J.; Chalaris, A.; Garbers, C.; Rose-John, S. ADAM17: A molecular switch to control inflammation and tissue regeneration. Trends Immunol. 2011, 32, 380–387. [Google Scholar] [CrossRef] [PubMed]
- Reiss, K.; Saftig, P. The “a disintegrin and metalloprotease” (ADAM) family of sheddases: Physiological and cellular functions. Semin. Cell Dev. Biol. 2009, 20, 126–137. [Google Scholar] [CrossRef] [PubMed]
- Edwards, D.R.; Handsley, M.M.; Pennington, C.J. The ADAM metalloproteinases. Mol. Aspects Med. 2008, 29, 258–289. [Google Scholar] [CrossRef]
- Simons, M.; Raposo, G. Exosomes—Vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 2009, 21, 575–581. [Google Scholar] [CrossRef]
- Pols, M.S.; Klumperman, J. Trafficking and function of the tetraspanin CD63. Exp. Cell Res. 2009, 315, 1584–1592. [Google Scholar] [CrossRef]
- Zhijun, X.; Shulan, Z.; Zhuo, Z. Expression and significance of the protein and mRNA of metastasis suppressor gene ME491/CD63 and integrin alpha5 in ovarian cancer tissues. Eur. J. Gynaecol. Oncol. 2007, 28, 179–183. [Google Scholar] [PubMed]
- Vences-Catalán, F.; Levy, S. Immune Targeting of Tetraspanins Involved in Cell Invasion and Metastasis. Front Immunol. 2018, 9, 1277. [Google Scholar] [CrossRef] [Green Version]
- Vences-Catalán, F.; Rajapaksa, R.; Srivastava, M.K.; Marabelle, A.; Kuo, C.C.; Levy, R.; Levy, S. Tetraspanin CD81 promotes tumor growth and metastasis by modulating the functions of T regulatory and myeloid-derived suppressor cells. Cancer Res. 2015, 75, 4517–4526. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hong, I.K.; Byun, H.J.; Lee, J.; Jin, Y.J.; Wang, S.J.; Jeoung, D.I.; Kim, Y.M.; Lee, H. The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways. J. Biol. Chem. 2014, 289, 15691–15704. [Google Scholar] [CrossRef] [Green Version]
- Wang, H.X.; Sharma, C.; Knoblich, K.; Granter, S.R.; Hemler, M.E. EWI-2 negatively regulates TGF-β signaling leading to altered melanoma growth and metastasis. Cell Res. 2015, 25, 370–385. [Google Scholar] [CrossRef] [Green Version]
- Théry, C.; Amigorena, S.; Raposo, G.; Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. 2006, 30, 3–22. [Google Scholar] [CrossRef] [PubMed]
CD81 | CD63 | CD9 | |||||||
---|---|---|---|---|---|---|---|---|---|
Size (nm) | GM-1 | GM-2 | GM-3 | GM-1 | GM-2 | GM-3 | GM-1 | GM-2 | GM-3 |
50 | 4.3 | 41.7 | −16.7 | 204 | 179 | 172.3 | 696.7 | 690.3 | 633.6 |
55 | −18 | 48.4 | −32.3 | 187 | 175 | 193 | 1536 | 1136.7 | 1335.7 |
60 | 5.4 | 26.3 | 32.4 | 120.7 | 103 | 92 | 1162.7 | 628.6 | 983.7 |
65 | 31 | 38.7 | 37.7 | 45 | 83.7 | 44.7 | 784.7 | 376.3 | 663.4 |
70 | 33.4 | 15 | 27.6 | 30.2 | 54.3 | 17.6 | 520 | 259.7 | 426 |
75 | 22.7 | 23.7 | 23 | 19.2 | 44 | 16 | 348 | 194 | 327 |
80 | 17 | 20.3 | 15.7 | 11.3 | 38.7 | 9.7 | 271.6 | 156.3 | 248.4 |
85 | 13.7 | 22.3 | 13.3 | 9 | 30.3 | 7 | 199 | 121 | 184.3 |
90 | 13 | 27.7 | 9.3 | 5.3 | 28.3 | 8.7 | 142.6 | 85 | 138 |
95 | 7.3 | 10 | 9 | 4.5 | 19.4 | 5 | 102 | 65 | 92.3 |
100 | 8.7 | 10.3 | 6 | 5.5 | 18.3 | 7.4 | 64.3 | 52.3 | 64.4 |
105 | 6.7 | 6.7 | 3.3 | 6.5 | 4.3 | 3.6 | 42.3 | 30 | 56.3 |
110 | 5.6 | 9 | 3 | 3.8 | 6.6 | 2.3 | 41 | 18.3 | 35 |
115 | 6 | 14.6 | 3.4 | 3.3 | 7.3 | 1.4 | 22 | 14.6 | 21 |
120 | 5 | 7.3 | 3.3 | 0.8 | 6.3 | 3.3 | 18.3 | 8.7 | 17.7 |
125 | 2 | 6.7 | 2.4 | 1.8 | 7.4 | 1.4 | 10.3 | 7 | 12.4 |
130 | 3.4 | 6.7 | 2.3 | 0.2 | 6.4 | 1.7 | 7.7 | 5.4 | 9 |
135 | 1.7 | 3 | 1.3 | 1 | 1 | −0.3 | 6 | 6 | 8.3 |
140 | 3 | 7 | 0.4 | 0.5 | 5 | 1 | 5.7 | 3 | 3.7 |
145 | 1.3 | 2.6 | 0.7 | 0 | −1.7 | 1 | 4.7 | 0.6 | 4.4 |
150 | 1 | 1.3 | 0.3 | 0 | 2.7 | 0.7 | 3.7 | 2 | 3 |
155 | 1 | 3.6 | 1 | −0.7 | 0.3 | 0.3 | 1 | 0.3 | 4.3 |
160 | 0.3 | 2.3 | 0.3 | 0 | 2.3 | 0.3 | 1.3 | 1 | 1.7 |
165 | 0.3 | 3 | 0.3 | 1.5 | 3.3 | 0 | 1.7 | 2.3 | 1 |
170 | 0.3 | 3.4 | 1.7 | 0.8 | 1 | 0.3 | 1.6 | 2.4 | 1.7 |
175 | 1 | 1.3 | 0.7 | 0 | 1 | 0 | 0.3 | 1.3 | 0.7 |
180 | 0 | 2 | 0.7 | −0.3 | 1.3 | 0 | 0.7 | 2 | 0 |
185 | 0.3 | 2.7 | 0 | 0 | 1.7 | 0 | 0 | 1.4 | 1 |
190 | 0 | 3 | 0.3 | 0 | 1.6 | 0 | 0 | 0.6 | 0.7 |
195 | 0.4 | −0.3 | 0 | −0.3 | 1.4 | 0 | −0.3 | −0.3 | 0.3 |
200 | −0.3 | 1.3 | 1 | −0.3 | 1 | 0.7 | 0.4 | 0.3 | 0.7 |
CD81 | CD63 | CD9 | |||||||
---|---|---|---|---|---|---|---|---|---|
Size (nm) | GM-1 | GM-2 | GM-3 | GM-1 | GM-2 | GM-3 | GM-1 | GM-2 | GM-3 |
50 | 4.3 | 41.7 | −16.7 | 204 | 179 | 172.3 | 696.7 | 690.3 | 633.6 |
55 | −18 | 48.4 | −32.3 | 187 | 175 | 193 | 1536 | 1136.7 | 1335.7 |
60 | 5.4 | 26.3 | 32.4 | 120.7 | 103 | 92 | 1162.7 | 628.6 | 983.7 |
65 | 31 | 38.7 | 37.7 | 45 | 83.7 | 44.7 | 784.7 | 376.3 | 663.4 |
70 | 33.4 | 15 | 27.6 | 30.2 | 54.3 | 17.6 | 520 | 259.7 | 426 |
75 | 22.7 | 23.7 | 23 | 19.2 | 44 | 16 | 348 | 194 | 327 |
80 | 17 | 20.3 | 15.7 | 11.3 | 38.7 | 9.7 | 271.6 | 156.3 | 248.4 |
85 | 13.7 | 22.3 | 13.3 | 9 | 30.3 | 7 | 199 | 121 | 184.3 |
90 | 13 | 27.7 | 9.3 | 5.3 | 28.3 | 8.7 | 142.6 | 85 | 138 |
95 | 7.3 | 10 | 9 | 4.5 | 19.4 | 5 | 102 | 65 | 92.3 |
100 | 8.7 | 10.3 | 6 | 5.5 | 18.3 | 7.4 | 64.3 | 52.3 | 64.4 |
105 | 6.7 | 6.7 | 3.3 | 6.5 | 4.3 | 3.6 | 42.3 | 30 | 56.3 |
110 | 5.6 | 9 | 3 | 3.8 | 6.6 | 2.3 | 41 | 18.3 | 35 |
115 | 6 | 14.6 | 3.4 | 3.3 | 7.3 | 1.4 | 22 | 14.6 | 21 |
120 | 5 | 7.3 | 3.3 | 0.8 | 6.3 | 3.3 | 18.3 | 8.7 | 17.7 |
125 | 2 | 6.7 | 2.4 | 1.8 | 7.4 | 1.4 | 10.3 | 7 | 12.4 |
130 | 3.4 | 6.7 | 2.3 | 0.2 | 6.4 | 1.7 | 7.7 | 5.4 | 9 |
135 | 1.7 | 3 | 1.3 | 1 | 1 | −0.3 | 6 | 6 | 8.3 |
140 | 3 | 7 | 0.4 | 0.5 | 5 | 1 | 5.7 | 3 | 3.7 |
145 | 1.3 | 2.6 | 0.7 | 0 | −1.7 | 1 | 4.7 | 0.6 | 4.4 |
150 | 1 | 1.3 | 0.3 | 0 | 2.7 | 0.7 | 3.7 | 2 | 3 |
155 | 1 | 3.6 | 1 | −0.7 | 0.3 | 0.3 | 1 | 0.3 | 4.3 |
160 | 0.3 | 2.3 | 0.3 | 0 | 2.3 | 0.3 | 1.3 | 1 | 1.7 |
165 | 0.3 | 3 | 0.3 | 1.5 | 3.3 | 0 | 1.7 | 2.3 | 1 |
170 | 0.3 | 3.4 | 1.7 | 0.8 | 1 | 0.3 | 1.6 | 2.4 | 1.7 |
175 | 1 | 1.3 | 0.7 | 0 | 1 | 0 | 0.3 | 1.3 | 0.7 |
180 | 0 | 2 | 0.7 | −0.3 | 1.3 | 0 | 0.7 | 2 | 0 |
185 | 0.3 | 2.7 | 0 | 0 | 1.7 | 0 | 0 | 1.4 | 1 |
190 | 0 | 3 | 0.3 | 0 | 1.6 | 0 | 0 | 0.6 | 0.7 |
195 | 0.4 | −0.3 | 0 | −0.3 | 1.4 | 0 | −0.3 | −0.3 | 0.3 |
200 | −0.3 | 1.3 | 1 | −0.3 | 1 | 0.7 | 0.4 | 0.3 | 0.7 |
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Wise, P.M.; Neviani, P.; Riwaldt, S.; Corydon, T.J.; Wehland, M.; Braun, M.; Krüger, M.; Infanger, M.; Grimm, D. Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space. Int. J. Mol. Sci. 2021, 22, 2132. https://doi.org/10.3390/ijms22042132
Wise PM, Neviani P, Riwaldt S, Corydon TJ, Wehland M, Braun M, Krüger M, Infanger M, Grimm D. Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space. International Journal of Molecular Sciences. 2021; 22(4):2132. https://doi.org/10.3390/ijms22042132
Chicago/Turabian StyleWise, Petra M., Paolo Neviani, Stefan Riwaldt, Thomas Juhl Corydon, Markus Wehland, Markus Braun, Marcus Krüger, Manfred Infanger, and Daniela Grimm. 2021. "Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space" International Journal of Molecular Sciences 22, no. 4: 2132. https://doi.org/10.3390/ijms22042132