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Sci Rep. 2016 Feb 26;6:22179. doi: 10.1038/srep22179.

Membrane type 1-matrix metalloproteinase induces epithelial-to-mesenchymal transition in esophageal squamous cell carcinoma: Observations from clinical and in vitro analyses.

Author information

1
Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
2
Department of Public Health, Medical School, Shihezi University School of Medicine, Shihezi 832002, Xinjiang, China.
3
Department of Clinical Laboratory, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China.
4
Department of Stomatology, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China.
5
Department of Thoracic and Cardiovascular Surgery, First Affiliated Hospital to Shihezi University School of Medicine, Shihezi 832008, Xinjiang, China.
6
Department of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
7
Department of Pathology, Beijing ChaoYang Hospital, Capital Medical University, Beijing, 100020, China.

Abstract

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.

PMID:
26916665
PMCID:
PMC4768157
DOI:
10.1038/srep22179
[Indexed for MEDLINE]
Free PMC Article

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