Preview

Advances in Molecular Oncology

Advanced search

Exosomal proteins as potential markers of multiple myeloma diagnostics

https://doi.org/10.17650/2313-805X-2018-5-1-60-69

Abstract

Background. Multiple myeloma (MM) is a hematologic malignancy of plasma cells. The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs). The role that EXs, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown. EXs as a source of markers for MM diagnostics are also not studied.

Objective: to use proteomic profiling of EXs as a tool to identify circulating tumor associated markers in MM patients.

Results. The proteome composition of EXs obtained from plasma of patients with MM and multiple sclerosis was studied for the first time. nano-HPLC–MS/MS analysis identified a total of 332 proteins in the EXs of both groups of patients and determined the proximity of their qualitative composition. For the first time, 12 differentially expressed proteins were detected, the levels of which were significantly increased in EXs from patients with MM. This allowed us to consider them as potential markers of the disease.

Conclusion. Proteomic analysis of EXs obtained from plasma of patients with MM is an important method for finding disease markers.

About the Authors

V. E. Shevchenko
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


A. S. Bryukhovetskiy
NeuroVita Clinic of Interventional and Restorative Neurology and Therapy
Russian Federation
23 Kashirskoe Shosse, Moscow 115478


M. V. Filatov
National Research Center “Kurchatov Institute”, B.P. Konstantinov Petersburg Nuclear Physics Institute
Russian Federation
1 Orlova Roshcha microdistrict, Gatchina, Leningrad Region 188300


V. S. Burdakov
National Research Center “Kurchatov Institute”, B.P. Konstantinov Petersburg Nuclear Physics Institute
Russian Federation
1 Orlova Roshcha microdistrict, Gatchina, Leningrad Region 188300


Z. N. Nikiforova
All-Russian State Center for Quality and Standardization of Veterinary Drugs and Feed
Russian Federation
5 Zvenigorodskoe Shosse, Moscow 123022


I. S. Bryukhovetskiy
School of Biomedicine, Far Eastern Federal University; National Scientific Center of Marine Biology, Far Eastern Branch of the Russian Academy of Sciences
Russian Federation

8 Sukhanova St., Vladivostok 690091

17 Pal’chevskogo St., Vladivostok 690059



Yu. D. Vasilets
K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology
Russian Federation
23 Akademika Skryabina St., Moscow 109472


T. I. Kushnir
K.I. Skryabin Moscow State Academy of Veterinary Medicine and Biotechnology
Russian Federation
23 Akademika Skryabina St., Moscow 109472


N. E. Arnotskaya
Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


References

1. Ferlay J., Soerjomataram I., Ervik M. et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide. IARC Cancer Base 2012;11:1–10.

2. Kumar S.K., Rajkumar S.V., Dispenzieri A. et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111(5):2516–20. DOI: 10.1182/blood-2007-10-116129. PMID: 17975015.

3. Roccaro A.M., Sacco A., Maiso P. et al. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J Clin Invest 2013;123(4):1542–55. DOI: 10.1172/JCI66517. PMID: 23454749.

4. Damiano J.S., Cress A.E., Hazlehurst L.A. et al. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 1999;93(5):1658–67. PMID: 10029595.

5. Thery C. Exosomes: secreted vesicles and intercellular communications. F1000 Biol Rep 2011;3:15. DOI: 10.3410/B3-15. PMID: 21876726.

6. Wang J., Hendrix A., Hernot S. et al. Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood 2014;124(4):555–66. DOI: 10.1182/ blood-2014-03-562439.PMID: 24928860.

7. Samsonov R., Burdakov V., Shtam T. et al. Plasma exosomal miR-21 and miR-181a differentiates follicular from papillary thyroid cancer. Tumour Biol 2016;37(9):12011–21. DOI: 10.1007/ s13277-016-5065-3. PMID: 27164936.

8. Bryukhovetskiy I., Shevchenko V. Molecular mechanisms of the effect of TGF-β1 on U87 human glioblastoma cells. Oncol Lett 2016;12(2):1581–90. DOI: 10.3892/ol.2016.4756. PMID: 27446475.

9. Pocsfalvi G., Stanly C., Vilasi A. et al. Mass spectrometry of extracellular vesicles. Mass Spectrom Rev 2015;35(1):3–21. DOI: 10.1002/mas.21457. PMID: 25705034.

10. Andreu Z., Yanez-Mo M. Tetraspanins in extracellular vesicle formation and function. Front Immunol 2014;5:442. DOI: 10.3389/fimmu.2014.00442. PMID: 25278937.

11. Paiva B., Gutierrez N.C., Chen X. et al. Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients. Leukemia 2012;26(8): 1862–9. DOI: 10.1038/leu.2012.42. PMID: 22333880.

12. Maecker H.T., Todd S.C., Levy S. The tetraspanin superfamily: molecular facilitators. FASEB J 1997;11(6):428–42. PMID: 9194523.

13. Stupack D.G., Cheresh D.A. Integrins and angiogenesis. Curr Top Dev Biol 2004;64:207–38. DOI: 10.1016/ S0070-2153(04)64009-9. PMID: 15563949.

14. Schroder H.M., Hoffmann S.C., Hecker M. et al. The tetraspanin network modulates MT1-MMP cell surface trafficking. Int J Biochem Cell Biol 2013;45(6):1133–44. DOI: 10.1016/ j.biocel.2013.02.020. PMID: 23500527.

15. Azmi A.S., Bao B., Sarkar F.H. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metast Rev 2013;32(3–4):623–42. DOI: 10.1007/s10555-013-9441-9. PMID: 23709120.

16. Kahlert C., Kalluri R. Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berl) 2013;91(4):431–7. DOI: 10.1007/s00109-013-1020-6. PMID: 23519402.

17. Harshman S.W., Canella A., Ciarlariello P.D. et al. Proteomic characterization of circulating extracellular vesicles identifies novel serum myeloma associated markers. J Proteomics 2016;136:89–98. DOI: 10.1016/ j.jprot.2015.12.016. PMID: 26775013.

18. Chen X., Yang T.T., Zhou Y. et al. Proteomic profiling of osteosarcoma cells identifies ALDOA and SULT1A3 as negative survival markers of human osteosarcoma. Mol Carcinog 2014;53(2)138–44. DOI: 10.1002/mc.21957. PMID: 22949271.

19. Seckinger A., Meissner T., Moreaux J. et al. Clinical and prognostic role of annexin A2 in multiple myeloma. Blood 2012;120(5):1087–94. DOI: 10.1182/ blood-2012-03-415588. PMID: 22705595.

20. Qi H., Liu S., Guo C. et al. Role of annexin A6 in cancer. Oncol Lett 2015;10(4):1947–52. DOI: 10.3892/ ol.2015.3498. PMID: 26622779.

21. Yan L., Zucker S., Toole B.P. Roles of the multifunctional glycoprotein, emmprin (basigin; CD147), in tumour progression. Thromb Haemost 2005;93(2):199–204. DOI: 10.1160/ TH04-08-0536. PMID: 15711733.

22. Yaccoby S. Advances in the understanding of myeloma bone disease and tumor growth. Br J Haematol 2010;149(3):311–21. DOI: 10.1111/j.1365-2141.2010.08141.x. PMID: 20230410.

23. Zdzisinska B., Walter-Croneck A., Kandefer-Szerszen M. Matrix metalloproteinases-1 and -2, and tissue inhibitor of metalloproteinase-2 production is abnormal in bone marrow stromal cells of multiple myeloma patients. Leuk Res 2008;32(11):1763–9. DOI: 10.1016/ j.leukres.2008.04.001. PMID: 18472160.

24. Bruce B., Khanna G., Ren L. et al. Expression of the cytoskeleton linker protein ezrin in human cancers. Clin Exp Metastasis 2007;24(2):69–78. DOI: 10.1007/s10585-006-9050-x. PMID: 17370041.

25. He J., Ma G., Qian J. et al. Interaction between ezrin and cortactin in promoting epithelial to mesenchymal transition in breast cancer cells. Med Sci Monit 2017;23:1583–96. PMID: 28364518.

26. Fraemohs L., Koenen R.R., Ostermann G. et al. The functional interaction of the beta 2 integrin lymphocyte function-associated antigen-1 with junctional adhesion molecule-A is mediated by the I domain. J Immunol 2004;173(10):6259–64. PMID: 15528364.

27. Zhang M., Luo W., Huang B. et al. Overexpression of JAM-A in non-small cell lung cancer correlates with tumor progression. PLoS One 2013;8(11):e79173. DOI: 10.1371/journal.pone.0079173. PMID: 24265754.

28. Kelly K.R., Espitia C.M., Zhao W. et al. Junctional adhesion molecule-A is overexpressed in advanced multiple myeloma and determines response to oncolytic reovirus. Oncotarget 2015;6(38):41275–89. DOI: 10.18632/ oncotarget.5753. PMID: 26513296.

29. Subramani D., Alahari S.K. Integrinmediated function of Rab GTPases in cancer progression. Mol Cancer 2010;9:312. DOI: 10.1186/ 1476-4598-9-312. PMID: 21143914.

30. Bai Z., Ye Y., Liang B. et al. Proteomicsbased identification of a group of apoptosisrelated proteins and biomarkers in gastric cancer. Int J Oncol 2011;38(2):375–83. DOI: 10.3892/ijo.2010.873. PMID: 21165559.

31. Lee D.H., Chung K., Song J.A. et al. Proteomic identification of paclitaxelresistance associated hnRNP A2 and GDI2 proteins in human ovarian cancer cells. J Proteome Res 2010;9(11):5668–76. DOI: 10.1021/pr100478u. PMID: 20858016.

32. Ma Y., Hendershot L.M. The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer 2004;4(12):966–77. DOI: 10.1038/ nrc1505. PMID: 15573118.

33. Lee A.S. The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci 2001;26(8):504–10. PMID: 11504627.

34. Ni M., Lee A.S. ER chaperones in mammalian development and human diseases. FEBS Lett 2007;581(19):3641–51. DOI: 10.1016/j.febslet.2007.04.045. PMID: 17481612.

35. Shuda M., Kondoh N., Imazeki N. et al. Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J Hepatol 2003;38(5):605–14. PMID: 12713871.

36. Dong D., Stapleton C., Luo B. et al. A critical role for GRP78/BiP in the tumor microenvironment for neovascularization during tumor growth and metastasis. Cancer Res 2011;71(8):2848–57. DOI: 10.1158/0008-5472.CAN-10-3151. PMID: 21467168.

37. Park T., Chen Z.P., Leavitt J. Activation of the leukocyte plastin gene occurs in most human cancer cells. Cancer Res 1994;54(7):1775–81. PMID: 8137292.

38. Foran E., McWilliam P., Kelleher D. et al. The leukocyte protein L-plastin induces proliferation, invasion and loss of E-cadherin expression in colon cancer cells. Int J Cancer 2006;118(8):2098–104. DOI: 10.1002/ijc.21593. PMID: 16287074.

39. Klemke M., Rafael M.T., Wabnitz G.H. et al. Phosphorylation of ectopically expressed L-plastin enhances invasiveness of human melanoma cells. Int J Cancer 2007;120(12):2590–9. DOI: 10.1002/ ijc.22589. PMID: 17290393.

40. Gao H., Sun B., Fu H. et al. PDIA6 promotes the proliferation of HeLa cells through activating the Wnt/β-catenin signaling pathway. Oncotarget 2016;7(33):53289–98. DOI: 10.18632/oncotarget.10795. PMID: 27462866.


Review

For citations:


Shevchenko V.E., Bryukhovetskiy A.S., Filatov M.V., Burdakov V.S., Nikiforova Z.N., Bryukhovetskiy I.S., Vasilets Yu.D., Kushnir T.I., Arnotskaya N.E. Exosomal proteins as potential markers of multiple myeloma diagnostics. Advances in Molecular Oncology. 2018;5(1):60-69. (In Russ.) https://doi.org/10.17650/2313-805X-2018-5-1-60-69

Views: 798


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2313-805X (Print)
ISSN 2413-3787 (Online)