Cardiac Derived Stromal Cells Inhibit Tumor Cell Proliferation: A Potential Role Of miR206

Stromal cells play an important role in control of proliferation and differentiation of stem cells and are a key component of the stem cell niche. Bone marrow (BM) stromal cells (also termed mesenchymal stem cells; MSC) have been extensively studied and shown to control differentiation of hematopoietic stem cells (HSCs) in part through secreted growth factors. Recent studies have demonstrated the presence of stromal cells in cardiac tissue, however the role of cardiac stromal cells (CStrC) is unclear. In this study we have compared human CStrCs to human BM-MSCs and demonstrate that CStrCs have a similar morphology and surface marker expression as BM-MSCs. To further characterize the CStrCs we performed micro array analysis of human CStrCs compared to human BM-MSCs. The CStrCs expressed a distinct cytokine and cytokine receptor profile compared to BM-MSC. In addition, a number of micro RNAs were expressed at very high levels in CStrCs compared to BM-MSC. Cardiac- associated microRNAs, including miR-1, miR-133a, and miR-206 were expressed at higher levels in CStrCs compared to BM-MSC. Given the lack of tumor development in cardiac tissue we hypothesized that CStrCs would fail to support tumor cell growth which has been described for BM-MSCs. Therefore, we cultured human tumor cell lines on CStrCs and compared the tumor cell proliferation to BM-MSCs. CStrCs inhibited the proliferation of a range of tumor cell lines including myeloid cell lines HL60, K562, myeloma cell lines U-266, RPMI 8266, ARP-1 and the B cell line Raji, while BM-MSCs supported the proliferation of tumor cells. Further we tested media conditioned by CStrCs and demonstrated inhibition of proliferation of both cell lines. Previous studies have implicated miR-206 in inhibition of proliferation of tumor cells and given the high levels of expression of miR-206 in CStrCs we hypothesize that miR-206 is a key player in the inhibitory effects of CStrCs and this effect is mediated via secreted molecules.