Paracrine signals of mesenchymal stem cells induce epithelial to mesenchymal transition in gastric cancer cells.

Abstract

Given the high similarity of phenotypical and secretory properties of mesenchymal stem cells and fibroblasts, this study investigated the possibility of inducing EMT process by mesenchymal stem cells. Annually, more than 13% of deaths worldwide occur due to cancer. One of the main reasons for the high mortality rate is due to the metastasis of cancer stem cells. Induction of metastasis occurs during the EMT process, which can also be stimulated by fibroblast cells. Mesenchymal stem cells (MSCs) were isolated and sub-cultured until passage 3 or 4. AGS cells were co-cultured with MSCs for 4 days. As the positive control group, AGS cells were treated with TGF-β (10ng/ml) for 48h. Finally, the mRNA expression level of Vimentin, β-catenin, Snail, and E-cadherin as the EMT pattern, were evaluated by RT-PCR technique. Our findings indicated that AGS cells' crosstalk with MSCs significantly upregulated fibroblast markers including Vimentin and Snail expression. However, no significant changes were identified for β-catenin gene expression. Additionally, AGS treatment with MSCs resulted in diminished E-cadherin in the targeted cells. Based on the results, the AGS cells crosstalk with MSCs activates induction of epithelial mesenchymal transition, which is confirmed through the elevation of Vimentin and Snail expression and reduction of E-cadherin expression as a specific epithelial marker. However, it seems that MSc was not effective on Wnt/ β-catenin signal gastric cancer cell line.