Bone marrow-derived mesenchymal stem cells promote angiogenesis and growth of breast and prostate tumors

      Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues, where they incorporate into the tumor stroma. This behavior of MSCs has been exploited as a tumor-targeting strategy for cell-based cancer therapy. However, the effects of MSCs on tumor growth are controversial. In this study, bone marrow-derived MSCs (BM-MSCs) were isolated and characterized. Effects of BM-MSCs on proliferation of mouse breast cancer cell 4T1 cells in vitro were analyzed. Both co-cultured with mice BM-MSCs (mBM-MSCs) and treatment with mBM-MSCs-conditioned medium enhanced the growth of 4T1 cells. Co-injection of 4T1 cells and mBM-MSCs into nude mice led to increased tumor size compared with injection of 4T1 cells alone. Similar experiments using human prostate cancer cell DU145 cells and human BM-MSCs (hBM-MSCs) instead of 4T1 cells and mBM-MSCs got consistent results. Compared with tumors induced by injection of tumor cells alone, blood vessel area was greater in tumors from co-injection of tumor cells with BM-MSCs, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. Furthermore, both conditioned medium from hBM-MSCs alone and co-cultures of hBM-MSCs with DU145 cells were able to promote tube formation ability of human umbilical vein endothelial cells (HUVEC). When hBM-MSCs exposed to DU145 cells environment, the expression of markers associated with neovascularization (MIP-2, VEGF, TGF-β and IL6) were increased. Collectively, these findings indicated that BM-MSCs enhanced tumor growth both in vitro and in vivo. The promotion effect may partly attribute to the increased expression of pro-angiogenic factors in BM-MSCs in tumor microenvironment and subsequent enhancement in angiogenesis and tumor growth. Better understanding of the underlying mechanisms of interaction between tumor cells and MSCs could lead to establishment of new therapeutic approaches.
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