Membrane type-2 matrix metalloproteinases improve the progression of renal cell cancer

膜型2基质金属蛋白酶促进肾细胞癌进展

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作者:Yiming Chen, Hao Lu, Ding Tao, Min Fan, Qianfeng Zhuang, Zhaoyu Xing, Zhen Chen, Xiaozhou He

Abstract

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which involved in the degradation of extracellular matrix (ECM) and basement membrane (BM), and associated with tumor invasion and metastasis. Membrane type-2 MMP (MT2-MMP) is a member of MT-MMPs subgroup, and is supposed to be an important step for cancer invasion and metastasis. However, the roles of MT2-MMP in human renal cell carcinoma (RCC) remain unknown. In present study, we identified the roles of MT2-MMP in renal cancer progression by MT2-MMP suppression and overexpression in ACHN cells, which expressed highest level of MT2-MMP and lowest level of MT1-MMP in three kinds of renal cancer cells (786-0, ACHN, OS-RC-2). We found that the expression of MMP-2 could be regulated by MT2-MMP suppression or overexpression in ACHN cells, and both adhesion and invasive activities of ACHN cells were suppressed with MT2-MMP siRNA transfection. In addition, we found that MT2-MMP could increase ACHN cell proliferation, and inhibit cell apoptosis. In vitro tumor growth experiment showed that MT2-MMP could increase clone formation of ACHN cells. The results indicated that MT2-MMP could promoter renal cancer cell invasion and adhesion by activating the expression of MMP2, and stimulate tumor growth of renal cancer.

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