Mesenchymal Stromal Cells-Derived β2-Microglobulin Promotes Epithelial-Mesenchymal Transition of Esophageal Squamous Cell Carcinoma Cells

间充质基质细胞衍生的β2微球蛋白促进食管鳞状细胞癌细胞上皮-间质转化

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作者:Junjie Wang, Weilin Yang, Tao Wang, Xiaoyong Chen, Jiancheng Wang, Xiaoran Zhang, Chuang Cai, Beilong Zhong, Jiabin Wu, Zhenguang Chen, Andy Peng Xiang, Weijun Huang

Abstract

Mesenchymal stromal cells (MSCs) have been considered as one of the pivotal type of cells composing the tumor microenvironment. Although contact-dependent mechanisms and paracrine factors are thought to collaborate in governing the MSCs-based effects on tumors progression, the underlying mechanisms remain largely unknown. In particular, the involvement of MSCs-derived cytokines in the epithelial-mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) has not been clarified. In this study, we observed that β2-Microglobulin (B2M) is highly expressed in MSCs but scarcely in ESCC cells. Based on the previously described EMT promoting effect of B2M, we investigated the in vitro effect of MSCs-derived B2M on the EMT of ESCC cells, and discovered its subsequent enhancing effects on cell mobility and tumor-initiation. Further xenograft transplantation experiments confirmed the in vivo induction of tumor-initiation by MSCs-derived B2M. Noteworthy, we showed that the B2M expression positively correlated with poor prognosis. The fact that B2M is primarily expressed by the stroma of the ESCC tissue strengthens our hypothesis that in ESCC, MSCs-derived B2M promotes tumor-initiation and invasion via enhancing EMT, resulting in an adverse prognosis for the patients. Our results will be valuable for the prediction of the development and treatment of ESCC.

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