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The Effect of Multipotent Mesenchymal Stromal Cell Derivatives on the Properties of Breast Cancer Cells in vitro and in vivo

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Abstract

The effects of multipotent mesenchymal stromal cell (MMSC) derivatives on breast cancer cells have been studied in vitro and in vivo. A cytostatic effect of substances produced by human bone marrow MMSCs on the tumor cell population and the inhibition of tumor cell migration into the suspension fraction in vitro were demonstrated. These phenomena were accompanied by upregulation of tumor-associated marker expression: cytokeratin and EpCAM expression was upregulated in 2D and 3D cell cultures and vimentin expression was upregulated in 3D cultures. A single injection of mouse bone marrow MMSC lysate into the experimental animals suppressed tumor growth in thigh muscles. Moreover, this treatment contributed to the preservation of muscle tissue integrity and the normalization of biochemical parameters of the blood in animals that received grafts of Ehrlich adenocarcinoma tumor cells.

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References

  1. Albini, A., Bruno, A., Gallo, C., Pajardi, G., Noonan, D.M., and Dallaglio, K., Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity, Connect. Tissue Res., 2015, vol. 56, no. 5, pp. 414–225. doi 10.3109/03008207.2015.1066780

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Soysal, S.D., Tzankov, A., and Muenst, S.E., Role of the tumor microenvironment in breast cancer, Pathobiology, 2015, vol. 82, nos. 3–4, pp. 142–152. doi 10.1159/000430499

    Article  PubMed  CAS  Google Scholar 

  3. Pein, M. and Oskarsson, T., Microenvironment in metastasis: roadblocks and supportive niche, Am. J. Physiol. Cell Physiol., 2015, vol. 309, no. 10, pp. 627–638. doi 10.1152/ajpcell.00145.2015

    Article  CAS  Google Scholar 

  4. Karnoub, A.E., Dash, A.B., Vo, A.P., Sullivan, A., Brooks, M.W., Bell, G.W., Richardson, A.L., Polyak, K., Tubo, R., and Weinberg, R.A., Mesenchymal stem cells within tumour stroma promote breast cancer metastasis, Nature, 2007, vol. 449, no. 7162, pp. 557–563. doi 10.1038/nature06188

    Article  PubMed  CAS  Google Scholar 

  5. Hematti, P. and Keating, A., Mesenchymal Stromal Cells: Biology and Clinical Applications, London: Humana, 2013, pp. 3–16.

    Book  Google Scholar 

  6. Zhang, C., Yang, S.-J., Wen, Q., Zhong, J.F., Chen, X.-L., Stucky, A., Press, M.F., and Zhang, X., Human-derived normal mesenchymal stem/stromal cells in anticancer therapies, J. Cancer, 2017, vol. 8, no. 1, pp. 85–96. doi 10.7150/jca.16792

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Seke, E.P., Vecchio, L., and Nwabo, K.A., Signaling pathways in chronic myeloid leukemia and leukemic stem cell maintenance: key role of stromal microenvironment, Cell Signal., 2012, vol. 24, no. 9, pp. 1883–1888. doi 10.1016/j.cellsig.2012.05.015

    Article  CAS  Google Scholar 

  8. Mirsha, P.J. and Merlino, G., A traitor in our midst: mesenchymal stem cells contribute to tumor progression and metastasis, Future Oncol., 2008, vol. 4, no. 6, pp. 745–749. doi 10.2217/14796694.4.6.745

    Article  Google Scholar 

  9. Pacioni, S., D’Alessandris Q.G., Giannetti S., Morgante L., Cocce V., Bonomi A., Buccarelli M., Pascucci L., Alessandri G., Pessina A., Ricci-Vitiani L., Falchetti M.L., Pallini R. Human mesenchymal stromal cells inhibit tumor growth in orthotopic glioblastoma xenografts, Stem. Cell Res. Ther., 2017, vol. 8, no. 1. doi 10.1186/s13287-017-0516-3

    Google Scholar 

  10. Klopp, A.H., Gupta, A., Spaeth, E., Andreeff, M., and Marini, F., 3rd, Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth?, Stem. Cells, 2011, vol. 29, no. 1, pp. 11–19. doi 10.1002/stem.559

    Article  PubMed  CAS  Google Scholar 

  11. Ohlsson, L.B., Varas, L., Kjellman, C., Edvardsen, K., and Lindvall, M., Mesenchymal progenitor cell-mediated inhibition of tumor growth in vivo and in vitro in gelatin matrix, Exp. Mol. Pathol., 2003, vol. 75, no. 3, pp. 248–255.

    Article  PubMed  CAS  Google Scholar 

  12. Otsu, K., Das S., Houser S.D., Quadri S.K., Bhattacharya S., Bhattacharya J. Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells, Blood, 2009, vol. 113, no. 18, pp. 4197–205. doi 10.1182/blood-2008-09-176198

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Khakoo, A.Y., Pati, S., Anderson, S.A., Reid, W., Elshal, M.F, Rovira, I.I., Nguyen, A.T., Malide, D., Combs, C.A., Hall, G., Zhang, J., Raffeld, M., Rogers, T.B., Stetler-Stevenson, W., Frank, J.A., Reitz, M., and Finkel, T., Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma, J. Exp. Med., 2006, vol. 203, no. 5, pp. 1235–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Dasari, V.R., Kaur, K., Velpula, K.K., Gujrati, M., Fassett, D., Klopfenstein, J.D., Dinh, D.H., and Rao, J.S., Upregulation of PTEN in glioma cells by cord blood mesenchymal stem cells inhibits migration via downregulation of the PI3K/Akt pathway, PLoS One, 2010, vol. 5, no. 4. e10350.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Dasari, V.R., Velpula, K.K., Kaur, K., Fassett, D., Klopfenstein, J.D., Dinh, D.H., Gujrati, M., and Rao, J.S., Cord blood stem cell-mediated induction of apoptosis in glioma downregulates X-linked inhibitor of apoptosis protein (XIAP), PLoS One, 2010, vol. 5, no. 7. e11813. doi 10.1371/journal.pone.0011813

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Lu, Y.R., Yuan, Y., Wang, X.J., Wei, L.L., Chen, Y.N., Cong, C., Li, S.F., Long, D., Tan, W.D., Mao, Y.Q., Zhang, J., Li, Y.P., and Cheng, J.Q., The growth inhibitory effect of mesenchymal stem cells on tumor cells in vitro and in vivo, Cancer Biol. Ther., 2008, vol. 7, no. 2, pp. 245–51.

    Article  PubMed  CAS  Google Scholar 

  17. Ma, Y., Hao, X., Zhang, S., and Zhang, J., The in vitro and in vivo effects of human umbilical cord mesenchymal stem cells on the growth of breast cancer cells, Breast Cancer Res. Treat., 2011, vol. 133, no. 2, pp. 473–485. doi 10.1007/s10549-011-1774-x

    Article  PubMed  CAS  Google Scholar 

  18. Melzer, C., Yang, Y., and Hass, R., Interaction of MSC with tumor cells, Cell Commun. Signal., 2016, vol. 14, no. 1. doi 10.1186/s12964-016-0143-0

    Google Scholar 

  19. Trivanovic, D., Krstic, J., Djordjevic, I.O., Mojsilovic, S., Santibanez, J.F., Bugarski, D., and Jaukovic, A., The roles of mesenchymal stromal/stem cells in tumor microenvironment associated with inflammation, Mediators Inflamm., 2016, vol. 2016, pp. 1–14. doi.org/doi 10.1155/2016/7314016

    Article  CAS  Google Scholar 

  20. Zhu, W., Xu, W., Jiang, R., Qian, H., Chen, M., Hu, J., Cao, W., Han, C., and Chen, Y., Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo, Exp. Mol. Pathol., 2006, vol. 80, no. 3, pp. 267–274. doi 10.1016/j.yexmp.2005.07.004

    Article  PubMed  CAS  Google Scholar 

  21. Hass, R. and Otte, A., Mesenchymal stem cells as allround supporters in a normal and neoplastic microenvironment, Cell Commun. Signal., 2012, vol. 10, no. 1. doi 10.1186/1478-811X-10-26

    Google Scholar 

  22. Hui, L. and Chen, Y., Tumor microenvironment: sanctuary of the devil, Cancer Lett., 2015, vol. 368, no. 1, pp. 7–13. doi 10.1016/j.canlet.2015.07.039

    Article  PubMed  CAS  Google Scholar 

  23. Horwitz, E.M., Le Blanc, K., Dominici, M., Mueller, I., Slaper-Cortenbach, I., Marini, F.C., Deans, R.J., Krause, D.S., and Keating, A., Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement, Cytotherapy, 2005, vol. 7, no. 5, pp. 393–395. doi 10.1080/14653240500319234

    Article  PubMed  CAS  Google Scholar 

  24. Bjerkvig, R., Spheroid Culture in Cancer Research, London: Taylor & Francis, 1991.

    Google Scholar 

  25. Marcucci, F., Stassi, G., and DeMaria, R., Opinion: epithelial–mesenchymal transition: new target in anticancer drug discovery, Nat. Rev. Drug. Discov., 2016, vol. 15, no. 5, pp. 311–325. doi 10.1038/nrd.2015.13

    Article  PubMed  CAS  Google Scholar 

  26. Thiery, J.P., TeckLim C., Tumor dissemination: an EMT affair, Cancer Cell, 2013, vol. 23, no. 3, pp. 272–273. doi.org/doi 10.1016/j.ccr.2013.03.004

    Article  PubMed  CAS  Google Scholar 

  27. Kalluri, R. and Weinberg, R.A., The basis of epithelial–mesenchymal transition, J. Clin. Invest., 2009, vol. 119, no. 6, pp. 1420–1428. doi 10.1172/JCI39104

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Gostner, J.M., Fong, D., Wrulich, O.A., Lehne, F., Zitt, M., Hermann, M., Krobitsch, S., Martowicz, A., Gastl, G., and Spizzo, G., Effects of EpCAM overexpression on human breast cancer cell lines, BMC Cancer, 2011, vol. 11. doi 10.1186/1471-2407-11-45

  29. De Miguel, M.P., Fuentes-Julian, S., Blazquez-Martinez, A., Pascual, C.Y., Aller, M.A., Arias, J., and Arnalich-Montiel, F., Immunosuppressive properties of mesenchymal stem cells: advances and applications, Curr. Mol. Med., 2012, vol. 12, no. 5, pp. 574–591. doi 10.2174/156652412800619950

    Article  PubMed  Google Scholar 

  30. Tran, C. and Damaser, M.S., Stem cells as drug delivery methods: Application of stem cell secretome for regeneration, Adv. Drug. Deliv. Rev., 2005, vols. 82–83, pp. 1–11. doi 10.1016/j.addr.2014.10.007

    Google Scholar 

  31. Cortes-Dericks, L., Froment, L., Kocher, G., and Schmid, R.A., Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines, Stem. Cell Res. Ther., 2016, vol. 7. doi 10.1186/s13287-016-0282-7

  32. Gauthaman, K., Yee, F.C., Cheyyatraivendran, S., Biswas, A., Choolani, M., and Bongso, A., Human umbilical cord Wharton’s jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro, J. Cell Biochem., 2012, vol. 113, no. 6, pp. 2027–2039. doi 10.1002/jcb.24073

    Article  PubMed  CAS  Google Scholar 

  33. Fong, C.Y., Biswas, A., Subramanian, A., Srinivasan, A., Choolani, M., and Bongso, A., Human keloid cell characterization and inhibition of growth with human Wharton’s jelly stem cell extracts, J. Cell Biochem., 2014, vol. 115, no. 5, pp. 826–838. doi 10.1002/jcb.24724

    Article  PubMed  CAS  Google Scholar 

  34. Wu, S., Ju, G.Q., Du, T., Zhu, Y.J., and Liu, G.H., Microvesicles derived from human umbilical cord Wharton’s jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo, PLoS One, 2013, vol. 8, no. 4. e61366. doi 10.1371/journal.pone.0061366

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Tran, S.D., Liu, Y., Xia, D., Maria, O.M., Khalili, S., Wang, R.W., Quan, V.H., Hu, S., and Seuntjens, J., Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation, PLoS One, 2013, vol. 8, no. 4. e61632. doi 10.1371/journal.pone.0061632

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Biology and Medicine (Education and Research Center), Kyiv, Ukraine

    T. Herheliuk & L. Ostapchenko

  2. Department of Biotechnological Problems of Diagnostics, Institute of Cryobiology and Cryomedicine Problems, National Academy of Sciences of Ukraine, Kyiv, Ukraine

    O. Perepelytsina & M. Sydorenko

Authors
  1. T. Herheliuk
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  2. O. Perepelytsina
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  3. L. Ostapchenko
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  4. M. Sydorenko
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Correspondence to T. Herheliuk.

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Original Ukrainian Text © T. Herheliuk, O. Perepelytsina, L. Ostapchenko, M. Sydorenko, 2018, published in Tsitologiya i Genetika, 2018, Vol. 52, No. 4, pp. 54–67.

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Herheliuk, T., Perepelytsina, O., Ostapchenko, L. et al. The Effect of Multipotent Mesenchymal Stromal Cell Derivatives on the Properties of Breast Cancer Cells in vitro and in vivo. Cytol. Genet. 52, 283–293 (2018). https://doi.org/10.3103/S0095452718040035

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  • DOI: https://doi.org/10.3103/S0095452718040035

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