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 <0.05 were considered statistically significant. Results: In this study, the most effective chemoattractant that increases the rate of migration in the osteosarcoma cell line under both normoxic (P 0.02) and hypoxic (P 0.004) conditions have been found to be the chemoattractant obtained from the BMSC culture. Conclusion: Soluble factors secreted by BM-MSCs to micro-environment are highly effective chemoattractants for osteosarcoma, nevertheless the stem cells that have been co-cultured with the MG-63 decrease this behavior. These results could provide a new scientific approach to downregulate the metastasis induced by the effect of BM-MSCs.