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Exosomes of Malignant Tumors: Prospects of Omiсs Diagnostics

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Abstract—

Early detection of the disease, prediction of its course, and response to therapy are the main problems in the diagnostics and treatment of malignant tumors. They may be solved by means of identification of biomarkers secreted by tumor cells within extracellular vesicles, particularly, exosomes. The study of exosomal proteins attracts special attention, because exosomal proteins can contain information about tumor identity, and also represent a set of signaling molecules, regulating processes of tumor progression and growth. In addition, analysis of exosomes secreted into the extracellular space corresponds to the promising concept of a liquid biopsy. In this review, we have summarized the current information about molecular studies of exosomes from various types of malignant tumors, including colorectal cancer, lung cancer, ovary, prostate and breast cancers, with special emphasis on omics methods and have considered prospects for their use in diagnostics.

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REFERENCES

  1. Graves, L.E., Ariztia, E.V., Navari, J.R., Matzel, H.J., Stack, M.S., and Fishman, D.A., Cancer Res., 2004, vol. 64, no. 19, pp. 7045–7049.

    Article  CAS  Google Scholar 

  2. Al-Nedawi, K., Meehan, B., Kerbel, R.S., Allison, A.C., and Rak, J., Proc. Natl. Acad. Sci. USA, 2009, vol. 106, no. 10, pp. 3794–3799. https://doi.org/10.1073/pnas.0804543106

    Article  PubMed  Google Scholar 

  3. Ichim, T.E., Zhong, Z., Kaushal, S., Zheng, X., Ren, X., Hao, X., Joyce, J.A., Hanley, H.H., Riordan, N.H., Koropatnick, J., Bogin, V., Minev, B.R., Min, W.P., and Tullis R.H., J. Translat. Med., 2008, vol. 22, pp. 6–37. https://doi.org/10.1186/1479-5876-6-37

    Article  CAS  Google Scholar 

  4. Kosaka, N., Yoshioka, Y., Fujita, Y., and Ochiya, T., J. Clin. Invest., 2016, vol.126, no. 4, pp. 1163–1172. https://doi.org/10.1172/JCI81130

    Article  PubMed  PubMed Central  Google Scholar 

  5. Harding, C., Heuser, J., and Stahl, P., J. Cell Biol., 1983, vol. 97, no. 2, pp. 329–339.

    Article  CAS  Google Scholar 

  6. Pan, B. and Johnstone, R.M., Cell, 1983, vol. 33, no. 3, pp. 967–978.

    Article  CAS  Google Scholar 

  7. Raposo, G., Nijman, H.W., Stoorvogel, W., Liejendekker, R., Harding, C.V., Melief, C.J., and Geuze, H.J., J. Exp. Med., 1996, vol. 183, no. 3, pp. 1161–1172.

    Article  CAS  Google Scholar 

  8. Zitvogel, L., Regnault, A., Lozier, A., Wolfers, J., Flament, C., Tenza, D., Ricciardi-Castagnoli, P., Raposo, G., and Amigorena, S., Nat. Med., 1998, vol. 4, no. 5, pp. 594–600.

    Article  CAS  Google Scholar 

  9. Théry, C., Ostrowski, M., and Segura, E., Nat. Rev. Immunol., 2009, vol. 9, no. 8, pp. 581–593.

    Article  Google Scholar 

  10. Simons, M. and Raposo, G., Curr. Opin. Cell Biol., 2009, vol. 21, no. 4, pp. 575–581. https://doi.org/10.1016/j.ceb.2009.03.007

    Article  CAS  PubMed  Google Scholar 

  11. Harding, C.V., Heuser, J.E., and Stahl, P.D., J. Cell B-iol., 2013, vol. 200, no. 4, pp. 367–371. https://doi.org/10.1083/jcb.201212113

    Article  CAS  Google Scholar 

  12. Pan, B.T., Teng, K., Wu, C., Adam, M., and Johnstone, R.M., J. Cell Biol., 1985, vol. 101, no. 3, pp. 942–948.

    Article  CAS  Google Scholar 

  13. Lafourcade, C., Sobo, K., Kieffer-Jaquinod, S., Garin, J., and van der Goot, F.G., PLoS One, 2008, vol. 3, no. 7, e2758. https://doi.org/10.1371/journal.pone.0002758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kalani, A., Tyagi, A., and Tyagi, N., Molecular Neurobiology, 2014, vol. 49, no. 1, pp. 590–600. https://doi.org/10.1007/s12035-013-8544-1

    Article  CAS  PubMed  Google Scholar 

  15. Colombo, M., Raposo, G., and Théry, C., Annu. Rev. Cell Dev. Biol., 2014, vol. 30, no. 1, pp. 255–289.

    Article  CAS  Google Scholar 

  16. Ratajczak, J., Wysoczynski, M., Hayek, F., Janowska-Wieczorek, A., and Ratajczak, M.Z., Leukemia, 2006, vol. 20, no. 9, pp. 1487–1495.

    Article  CAS  Google Scholar 

  17. Valadi, H., Karin, E., and Apostolos, B., Lipid Insights, 2008, vol. 1, no. 6, pp. 27–40.

    Google Scholar 

  18. Hemler, M.E., Annu. Rev. Cell Dev. Biol., 2003, vol. 19, pp. 397–422.

    Article  CAS  Google Scholar 

  19. Hanson, P.I. and Cashikar, A., Annu. Rev. Cell Dev. Biold-., 2012, vol. 28, no. 1, pp. 337–362. https://doi.org/10.1146/annurev-cellbio-092910-154152

    Article  CAS  PubMed  Google Scholar 

  20. Wubbolts, R., Leckie, R.S., Peter, T., Veenhuizen, M., Schwarzmann, G., Möbius, W., Hoernschemeyer, J., Slot, J.W., Geuze, H.J., and Stoorvogel, W., J. Biol. Chem., 2003, vol. 278, pp. 10963–10972.

    Article  CAS  Google Scholar 

  21. Shushkova, N.A., Vavilov, N.E., Novikova, S.E., Farafonova, T.E., Tikhonova, O.V., Liao, P.C., and Zgoda, V.G., Biomed. Khimiya, 2018, vol. 64, no. 6, pp. 496–504. https://doi.org/10.18097/PBMC20186406496

    Article  CAS  Google Scholar 

  22. Mathivanan, S. and Simpson, R.J., Proteomics, 2009, vol. 9, no. 21, pp. 4997–5000. https://doi.org/10.1002/pmic.200900351

    Article  CAS  PubMed  Google Scholar 

  23. Tung, K., Ernstoff, M., Allen, C., and Shu, S., J. Immunol. Sci., 2019, vol. 3, no. 1, pp. 4–8. https://doi.org/10.29245/2578-3009/2019/1.1165

    Article  PubMed  PubMed Central  Google Scholar 

  24. Whiteside, T.L., J. Clin. Invest., 2016, vol. 126, no. 4, pp. 1216–1223. https://doi.org/10.1172/JCI81136

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shu, S., Yang, Y., Allen, C.L., Maguire, O., Minderman, H., Sen, A., Ciesielski, M.J., Collins, K.A., Bush, P.J., Singh, P., Wang, X., Morgan, M., Qu, J., Bankert, R.B., Whiteside, T.L., Wu, Y., and Ernstoff, M.S., Sci. Rep., 2018, vol. 8, no. 1, 12905. https://doi.org/10.1038/s41598-018-31323-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang, H., Deng, T., Liu, R., Bai, M., Zhou, L., Wang, X., Li, S., Wang, X., Yang, H., Li, J., Ning, T., Huang, D., Li, H., Zhang, L., Ying, G., and Ba, Y., Nat. Commun., 2017, vol. 8, 15016. https://doi.org/10.1038/ncomms15016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Beckler, M.D., Higginbotham, J.N., Franklin, J.L., Ham, A.J., Halvey, P.J., Imasuen, I.E., Whitwell, C., Li, M., Liebler, D.C., and Coffey, R.J., Mol. Cell. Proteomics, 2013, vol. 12, no. 2, pp. 343–355. https://doi.org/10.1074/mcp.M112.022806

    Article  CAS  Google Scholar 

  28. https://www.who.int/ru/news-room/fact-sheets/detail/ cancer.

  29. Whiteside, T.L., Exp. Rev. Mol. Diagn., 2015, vol. 15, no. 10, pp. 1293–310. https://doi.org/10.1586/14737159.2015.1071666

    Article  CAS  Google Scholar 

  30. Reclusa, P., Taverna, S., Pucci, M., Durendez, E., Calabuig, S., Manca, P., Serrano, M.J., Sober, L., Pauwels, P., Russo, A., and Rolfo, C., J. Thorac. Dis., 2017, vol. 9, no. 13, pp. 1373–1382. https://doi.org/10.21037/jtd.2017.10.67

    Article  Google Scholar 

  31. Alipoor, S.D., Mortaz, E., Varahram, M., Movassaghi, M., Kraneveld, A.D., Garssen, J., and Adcock, I.M., Frontiers Immunol., 2018, vol. 9, 819. https://doi.org/10.3389/fimmu.2018.00819

    Article  CAS  Google Scholar 

  32. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T., Science, 2002, vol. 294, no. 5543, pp. 853–858.

    Article  Google Scholar 

  33. Rabinowits, G., Gerçel-Taylor, C., Day, J.M., Taylor, D.D., and Kloecker, G.H., Clin. Lung Cancer, 2009, vol. 10, no. 1, pp. 42–46. https://doi.org/10.3816/CLC.2009.n.006

    Article  CAS  PubMed  Google Scholar 

  34. Yuwen, D.L., Sheng, B.B., Liu, J., Wenyu, W., Shu, Y.Q., Eur. Rev. Med. Pharmacol. Sci., 2017, vol. 21, no. 11, pp. 2650–2658.

    PubMed  Google Scholar 

  35. Yuan, D., Xu, J., Wang, J., Pan, Y., Fu, J., Bai, Y., Zhang, J., and Shao, C., Oncotarget, 2016, vol. 7, no. 22, pp. 32 707–32 722. https://doi.org/10.18632/oncotarget.9017

    Article  Google Scholar 

  36. Cazzoli, R., Buttitta, F., di Nicola, M., Malatesta, S., Marchetti, A., Rom, W.N., and Pass, H.I., J. Thorac. Oncol., 2013, vol. 8, no. 9, pp. 1156–1162. https://doi.org/10.1097/JTO.0b013e318299ac32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jin, X., Chen, Y., Chen, H., Fei, S., Chen, D., Cai, X., Cai, X., Liu, L., Lin, B., Su, H., Zhao, L., Su, M., Pan, H., Shen, L., Xie, D., and Xie C., Clin. Cancer Res., 2017, vol. 23, no. 17, pp. 5311–5319. https://doi.org/10.1158/1078-0432.CCR-17-0577

    Article  CAS  PubMed  Google Scholar 

  38. Huang, S.H., Qin, J., Li, Y., An, J., Zhang, J.H., Rong, J., Ye, S., Chinese Pharmacol. Bull., 2014, vol. 30, no. 8, pp. 1090–1095. https://doi.org/10.3109/07357907.2013.789905

    Article  CAS  Google Scholar 

  39. Sandfeld-Paulsen, B., Aggerholm-Pedersen, N., Baek, R., Jakobsen, K.R., Meldgaard, P., Folker-sen, B.H., Rasmussen, T.R., Varming, K., Jørgen-sen, M.M., and Sorensen, B.S., Mol. Oncol., 2016, vol. 10, no. 10, pp. 1595–1602. https://doi.org/10.1016/j.molonc.2016.10.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Clark, D.J., Fondrie, W.E., Yang, A., and Mao, L., J. Proteomics, 2016, vol. 133, pp. 161–169. https://doi.org/10.1016/j.jprot.2015.12.023

    Article  CAS  PubMed  Google Scholar 

  41. Park, J.O., Choi, D.Y., Choi, D.S., Kim, H.J., Kang, J.W., Jung, J.H., Lee, J.H., Kim, J., Freeman, M.R., Lee, K.Y., Gho, Y.S., and Kim, K.P., Proteomics, 2013, vol. 13, no. 14, pp. 2125–2134. https://doi.org/10.1002/pmic.201200323

    Article  CAS  PubMed  Google Scholar 

  42. Niu, L., Song, X., Wang, N., Xue, L., Song, X., and Xie, L., Cancer Sci., 2019, vol. 110, no. 1, pp. 433–442. https://doi.org/10.1111/cas.13862

    Article  CAS  PubMed  Google Scholar 

  43. Thanikachalam, K. and Khan, G., Nutrients, 2019, vol. 11, no. 1, e164. https://doi.org/10.3390/nu11010164

    Article  CAS  PubMed  Google Scholar 

  44. Teng, Y., Ren, Y., Hu, X., Mu, J., Samykutty, A., Zhuang, X., Deng, Z., Kumar, A., Zhang, L., Merchant, M.L., Yan, J., Miller, D.M., and Zhang, H.G., Nat. Commun., 2017, vol. 8, 14448. https://doi.org/10.1038/ncomms14448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mathivanan, S., Lim, J.W.E., Tauro, B.J., Ji, H., Moritz, R.L., and Simpson, R.J., Mol. Cell. Proteomics, 2010, vol. 9, no. 2, pp. 197–208. https://doi.org/10.1074/mcp.M900152-MCP200

    Article  CAS  PubMed  Google Scholar 

  46. Tauro, B.J., Greening, D.W., Mathias, R.A., Ji, H., Mathivanan, S., Scott, A.M., and Simpson, R.J., Methods, 2012, vol. 56, no. 2, pp. 293–304. https://doi.org/10.1016/j.ymeth.2012.01.002

    Article  CAS  PubMed  Google Scholar 

  47. Choi, D.S., Choi, D.Y., Hong, B., Jang, S., Kim, D.K., Lee, J., Kim, Y.K., Kim, K.P., and Gho, Y.S., J. Extracell. Vesicles, 2012, vol. 1, no. 1, 18704. https://doi.org/10.3402/jev.v1i0.18704

    Article  CAS  Google Scholar 

  48. Hannafon, B.N., Trigoso, Y.D., Calloway, C.L., Zhao, Y.D., Lum, D.H., Welm, A.L., Zhao, Z.J., Blick, K.E., Dooley, W.C., and Ding, W.Q., Breast Cancer Res., 2016, vol. 18, no. 1, 90. https://doi.org/10.1186/s13058-016-0753-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Chow, A., Zhou, W., Liu, L., Fong, M.Y., Champer, J., van Haute, D., Chin, A.R., Ren, X., Gugiu, B.G., Meng, Z., Huang, W., Ngo, V., Kortylewski, M., and Wang, S.E., Sci Rep., 2015, vol. 4, no. 1, 5750. https://doi.org/10.1038/srep05750

    Article  CAS  Google Scholar 

  50. Palazzolo, G., Albanese, N.N., di Cara, G., Gygax, D., Vittorelli, M.L., and Pucci-Minafra, I., Anticancer Res., 2012, vol. 32, no. 3, pp. 847–860.

    CAS  PubMed  Google Scholar 

  51. Brett, S.I., Lucien, F., Guo, C., Williams, K.C., Kim, Y., Durfee, P.N., Brinker, C.J., Chin, J.I., Yang, J., and Leong, H.S., Prostate, 2017, vol. 77, no. 13, pp. 1335–1343. https://doi.org/10.1002/pros.23393

    Article  CAS  PubMed  Google Scholar 

  52. Yang, C., Guo, W., Zhang, W., Bian, J., Yang, J., Zhou, Q., Chen, Y.P., Chen, M.K., Peng, W., Qi, T., Wang, C.Y., and Liu, C.D., Andrology, 2017, vol. 5, no. 5, pp. 1007–1015. https://doi.org/10.1111/andr.12412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Turay, D., Khan, S., Diaz Osterman, C., Curtis, M., Khaira, B., and Neidighi, J., Cancer Invest., 2016, vol. 34, no.1, pp. 1–11. https://doi.org/10.3109/07357907

    Article  CAS  PubMed  Google Scholar 

  54. Yi, H., Ye, J., Yang, X.M., Zhang, L.W., and Zhang, Z.G., Int. J. Clin. Exp. Pathol., 2015, vol. 8, no. 5, pp. 5062–5070.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Liang, B., Peng, P., Chen, S., Li, L., Zhang, M., Cao, D., Yang, J., Li, H., Gui, T., Li, X., and Shen, K., J. Proteomics, 2013, vol. 80, pp. 171–182. https://doi.org/10.1016/j.jprot.2012.12.029

    Article  CAS  PubMed  Google Scholar 

  56. Taylor, D.D. and Gerçel-Taylor, C., Gynecol. Oncol., 2008, vol. 110, no. 110, pp. 13–21. https://doi.org/10.1016/j.ygyno.2008.04.033

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

Own results described in Section 4 were obtained using the equipment available at the Core Facilities “The Human Proteome”, IBMC .

Funding

The study was supported by the Russian Science Foundation, project no. 19-75-00044.

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Authors and Affiliations

  1. Institute of Biomedical Chemistry, ul. Pogodinskaya 10, 119121, Moscow, Russia

    N. A. Shushkova, S. E. Novikova & V. G. Zgoda

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  1. N. A. Shushkova
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  2. S. E. Novikova
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Correspondence to N. A. Shushkova.

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Translated by A. Medvedev

Abbreviations used: CEA—cancer embryonic antigen; CRC—colorectal cancer; EGFR—epidermal growth factor receptor; ELISA—enzyme-linked immunosorbent assay; ESCRT—endosomal sorting complex; HPLC-MS/MS—high performance liquid chromatography coupled with tandem mass spectrometry; MRM—multiple reaction monitoring; MVs—microvesicles; NSCLC—non-small cell lung cancer; nSMase—sphingomyelinase; PCa—prostate cancer; PEG—polyethylene glycol; PSA—Prostate Specific Antigen; SILAC—Stable Isotope Labeling with Amino acids in Cell culture.

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Shushkova, N.A., Novikova, S.E. & Zgoda, V.G. Exosomes of Malignant Tumors: Prospects of Omiсs Diagnostics. Biochem. Moscow Suppl. Ser. B 14, 105–115 (2020). https://doi.org/10.1134/S1990750820020122

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