Limitations of Cross-Talk Between Osteosarcoma and Bone Marrow-Derived Mesenchymal Stem Cells

Abstract

Objectives: Metastasis is a multi-step process which leads the tumor cells to escape from primer tumor region due to their need to gain malign phenotypes. While the effect of bone marrow-derived mesenchymal stem cells upon metastasis is not certain, some studies point out bone marrow-derived mesenchymal stem cells BM-MSCs to have this ability due to cell-cell interaction, released cytokines, and organization with the extracellular matrix in the micro-environment. Cross-talk via soluble factors also shifts the metastatic character.Patients and Methods: In this study, the effects of mesenchymal stem cells on tumor behavior by creating different microenvironments in 3-dimensional 3D in vitro cancer model is analyzed. The BM-MSCs and osteosarcoma cells were co-cultured via hanging-drop modeled 3D structure in normoxic and hypoxic conditions, and the cross-talk was modeled to measure their chemoattractant effects. The invasion and migration rates were measured with xCELLigence DP real-time cell analysis system. Mann Whitney U Test was used to compare independent samples. All P-values

Keywords

• Osteosarcoma,MG-63,BM-MSCs,Metastasis,Cross-Talk

References

1. Siclari VA, Qin L. Targeting the osteosarcoma cancer stem cell. J Orthop Surg Res BioMed 2010;5:78. [CrossRef]
2. Longhi A, Errani C, De Paolis M, Mercuri M, Bacci G. Primary bone osteosarcoma in the pediatric age. State of the art. Cancer Treat Rev 2006;32:423–436. [CrossRef]
3. Tang N, Song WX, Luo J, Haydon RC, He TC. Osteosarcoma development and stem cell differentiation. Clin Orthop Relat Res 2008;466:2114–2130. [CrossRef]
4. Caplan AI. The mesengenic process. Clin Plast Surg 1994;3:429–435.
5. Wagner W, Ho AD. Mesenchymal Stem Cell Preparations-Comparing Apples and Oranges. Stem Cell Rev 2007;3:239–248. [CrossRef]
6. Robado de Lope L, Alcíbar OL, Amor López A, Hergueta-Redondo M, Peinado H. Tumour-adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles. Philos Trans R Soc Lond B Biol Sci 2018;373:20160485. [CrossRef]
7. Peinado H, Zhang H, Matei I, et al. Pre-metastatic niches: organ- speciŞc homes for metastases. Nat Rev Cancer 2017;5:302–317. [CrossRef]
8. Mishra PJ, Mishra PJ, Humeniuk R, et al. Carcinoma-associated Şbroblast-like differentiation of human mesenchymal stem cells. Cancer Res 2008;68:4331–4339. [CrossRef]

9. Hass R, Otte A. Mesenchymal stem cells as all-round supporters in a normal and neoplastic microenvironment. Cell Commun Signal 2012;10:26. [CrossRef]
10. Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis. Cancer Cell 2016;30:836–848. [CrossRef]
11. Simmons PJ, Torok-Storb B. IdentiŞcation of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Blood 1991;78:55–62.
12. Ridge SM, Bhattacharyya D, Dervan E, et al. Secreted factors from metastatic prostate cancer cells stimulate mesenchymal stem cell transition to a pro-tumourigenic ‘activated’ state that enhances prostate cancer cell migration. Int J Cancer 2018;142:2056–2067. [CrossRef]
13. Jones E, McGonagle D. Human Bone Marrow Mesenchymal Stem cells in vivo. Rheumatology (Oxford) 2008;47:126–131. [CrossRef]
14. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2002;2:569–579. [CrossRef]
15. 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. [CrossRef]
16. Alfranca A, Martinez-Cruzado L, Tornin J, et al. Bone microenvironment signals in osteosarcoma development. Cell Mol Life Sci 2015;72:3097–3113. [CrossRef]
17. El-Badawy A, Ghoneim MA, Gabr MM, et al. Cancer cell-soluble factors reprogram mesenchymal stromal cells to slow cycling, chemoresistant cells with a more stem-like state. Stem Cell Res Ther 2017;8:254. [CrossRef]
18. Tu B, Du L, Fan QM, Tang Z, Tang TT. STAT3 activation by IL-6 from mesenchymal stem cells promotes the proliferation and metastasis of osteosarcoma. Cancer Lett 2012;325:80–88. [CrossRef]
19. Zhang P, Dong L, Yan K, et al. CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF. Oncol Rep 2013;30:1753–1761. [CrossRef]
20. Bian ZY, Fan QM, Li G, Xu WT, Tang TT. Human mesenchymal stem cells promote growth of osteosarcoma: Involvement of interleukin-6 in the interaction between human mesenchymal stem cells and Saos- 2. Cancer Sci 2010;101:2554–2560. [CrossRef]
21. Zhang P, Dong L, Long H, et al. Homologous mesenchymal stem cells promote the emergence and growth of pulmonary metastases of the rat osteosarcoma cell line UMR-106. Oncol Lett 2014;8:127–132. [CrossRef]
22. Avnet S, Di Pompo G, Chano T, et al. Cancer-associated mesenchymal stroma fosters the stemness of osteosarcoma cells in response to intratumoral acidosis via NF-κB activation. Int J Cancer 2017;140:1331–1345. [CrossRef]
23. Mandel K, Yang Y, Schambach A, Glage S, Otte A, Hass R. Mesenchymal Stem Cells Directly Interact with Breast Cancer Cells and Promote Tumor Cell Growth In Vitro and In Vivo. Stem Cells Dev 2013;22:3114–3127. [CrossRef]
24. Zhang T, Lee YW, Rui YF, Cheng TY, Jiang XH, Li G. Bone marrow- derived mesenchymal stem cells promote growth and angiogenesis of breast and prostate tumors. Stem Cell Res Ther 2013;4:70. [CrossRef]
25. Hazan RB, Phillips GR, Qiao RF, Norton L, Aaronson SA. Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis. J Cell Biol 2000;148:779–790. [CrossRef]
26. Lammens T, Swerts K, Derycke L, et al. N-Cadherin in Neuroblastoma Disease: Expression and Clinical SigniŞcance. PLoS One 2012;7:e31206. [CrossRef]
27. Zhuo H, Jiang K, Dong L, et al. Overexpression of N-cadherin is correlated with metastasis and worse survival in colorectal cancer patients. Chinese Sci Bull 2013;58:3529–3534. [CrossRef]
28. Rai H, Ahmed J. N-Cadherin: A Marker of Epithelial to Mesenchymal Transition in Tumor Progression. Internet J Oncol 2014;10. Available at: https://print.ispub.com/api/0/ispub-article/14796
29. Fang S, Yu L, Mei H, et al. Cisplatin promotes mesenchymal- like characteristics in osteosarcoma through Snail. Oncol Lett 2016;12:5007–5014. [CrossRef]
30. Duval K, Grover H, Han L-H, et al. Modeling Physiological Events in 2D vs 3D Cell Culture. Physiology (Bethesda) 2017;32:266–277. [CrossRef]
31. Rahim S, Üren A. A real-time electrical impedance based technique to measure invasion of endothelial cell monolayer by cancer cells. J Vis Exp 2011;50. [CrossRef]
32. Liu Y, Feng Y, Liu H, Wu J, Tang Y, Wang Q. Real-time assessment of platinum sensitivity of primary culture from a patient with ovarian cancer with extensive metastasis and the platinum sensitivity enhancing effect by metformin. Oncol Lett 2018;16:4253–4262. [CrossRef]