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Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of
availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home
in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment.
Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about
phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting
results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor
microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer
stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among
multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic
environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as
communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is
the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new
combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and
cancer cells for treating breast cancer.