Suppressive Effect Of Human Umbilical Mesenchymal Stem Cells On Esophageal Cancer Cells

1sophageal cancer (EC) is a major health problem in China and some area of the world and the traditional therapies are often frustrating. Recently, human mesenchymal stem cells have been isolated from many tissues and applied in damaged tissue repair or regenerative medicine. The discovery that mesenchymal stem cells (MSCs) are recruited into tumors has led to a great deal of interest over the past decade in the function of MSCs in tumors. To address this, investigators have used a variety of tumor models in which MSCs are added exogenously to determine their impact on tumor development. Interestingly, many studies have reported contradicting results; with some investigators finding that MSCs promote tumor growth and others reporting that MSCs inhibit tumor growth. However, little is known about the underlying molecular mechanisms and understanding these is crucial, both to safely develop MSCs as a therapeutic tool or to advance our understanding of the role of tumor stroma in care ino genesis.In this investigation, firstly, we describe the ability of un-engineered human umbilical cord Wharton's jelly derived mesenchymal stem cells (hMSCs) can be tropism to inhibit the EC cells in vitro and the mechanism might include cell fusion.Then, we used an induced fusion model to explore the mechanism of the suppression. After hMSCs were fused with ECs, the hybrids were sorted by FACS and screened with surface marker expression. Then, declined cell growth, increased apoptosis and suppressed tumorigenicity were observed in hybrids. We compared their gene expression profiles and found that fusion induced activation of apoptosis and immunomodulatory is likely to be important for the anticancer effects of hMSCs. Furthermore, the expression of DUSP6/MKP3 of MAPK pathway was increased strikingly and the exogenous overexpression confirmed the growth suppression. Moreover, the acquired expression of mesenchymal markers while incapable of induced differentiation suggested that fusion induced benign transdifferentiation rather than pluripotent reprogramming likely to account for the suppression in part.At last, we investigated the potential suppressive effect of hMSCs on xenograft model of ECs in vivo. Although we failed to track the tropism of hMSCs to tumour tissue of ECs, the significant suppressive effect come from inoculation of mixed hMSCs and ECs (5:1) along with system administration through tail vain than mixed inoculation or system administration solely.Our findings demonstrate that hMSCs can inhibit malignant phenotypes of EC cells through induced cell fusion without potentially cancerous reprogramming in vitro and a conditioned suppressive effect in vivo. These results shed light on the fusion mechanism of anticancer stem cell therapy and also point to DUSP6 as a potential molecular target for esophageal cancer.