Membrane type 1-matrix metalloproteinase (MT1-MMP) is associated with enhanced tumorigenicity in many cancers. A recent study has revealed that MT1-MMP induces epithelial-to-mesenchymal transition (EMT) in prostate and breast cancer cells.
However, its role in esophageal squamous cell carcinoma (ESCC) has not been studied. Here, we investigated the role of MT1-MMP in the dissemination of ESCC. Expression of MT1-MMP was detected by immunohistochemistry and tissue microarray in 88 Kazakh ESCC patients. Western blotting was performed to detect endogenous and overexpressed exogenous MT1-MMP in the Eca109 and Eca9706 cell lines, respectively. Transwell assay was used to estimate MT1-MMP-induced invasion and metastasis. EMT-associated proteins were detected by immunohistochemistry and western blotting. The associations between the expression of MT1-MMP and EMT-associated proteins with clinicopathologic parameters were analyzed. Overexpression of MT1-MMP was confirmed in Kazakh ESCC patients. MT1-MMP levels were found to be correlated with the depth of tumor infiltration. MT1-MMP induced EMT in ESCC both in vivo and in vitro, N-cadherin and Vimentin expression was upregulated upon MT1-MMP transfection into cells. However, E-cadherin was found to be downregulated. MT1-MMP-induced EMT led to increase migration and invasion in ESCC cell lines. In conclusion, our results suggest that MT1-MMP promotes ESCC invasion and metastasis.
Scientific reports. 2016 Feb 26*** epublish ***
Lijuan Pang, Qiuxiang Li, Shugang Li, Jianwei He, Weiwei Cao, Jiaojiao Lan, Bin Sun, Hong Zou, Chengyan Wang, Ruixue Liu, Cuilei Wei, Yutao Wei, Yan Qi, Jianming Hu, Weihua Liang, Wen Jie Zhang, Mei Wan, Feng Li
Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Public Health, Medical School, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Clinical Laboratory, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Stomatology, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China., Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.