title: Overexpression of membrane-type 2 matrix metalloproteinase induced by hypoxia-inducible factor-1α in pancreatic cancer: Implications for tumor progression and prognosis.
abstract: Membrane-type 2 matrix metalloproteinase (MT2-MMP) has been identified as a powerful modulator of the pericellular environment that promotes tumor invasion and metastasis. In this study, we investigated the association of MT2-MMP and hypoxia-inducible factor-1α (HIF-1α) expression in pancreatic cancer with regard to their clinical prognostic significance. Of the tissue specimens obtained from the 78 patients included in this study, 46 (59%) were found to be positive for MT2-MMP immunostaining and MT2-MMP expression was colocalized with HIF-1α in pancreatic cancer. Using the Spearman's rank analysis, the protein and mRNA expression level of MT2-MMP was found to be significantly correlated with HIF-1α and CD34-microvascular density in pancreatic cancer. Furthermore, the expression of MT2-MMP in response to hypoxia was increased in a time-dependent manner and the promoter luciferase reporter revealed upregulation of MT2-MMP expression induced by HIF-1α in pancreatic cancer cells. Moreover, the Cox regression model indicated that MT2-MMP was an independent prognostic factor in patients with pancreatic cancer. Our results demonstrated that the overexpression of MT2-MMP was induced by HIF-1α in response to hypoxia and was an independent prognostic factor for pancreatic cancer progression.
authors.affiliation: Organ Transplant Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China ; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China.
authors.forename: Shi-Kai
authors.initials: SK
authors.lastname: Zhu
authors.affiliation: Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China ; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Organ Transplant Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China ; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Wu
authors.affiliation: Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Fan
authors.affiliation: Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Jiong-Xin
authors.initials: JX
authors.lastname: Xiong
authors.affiliation: Organ Transplant Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China ; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, P.R. China.
authors.forename: Hong-Ji
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: He-Shui
authors.initials: HS
authors.lastname: Wu
keywords: hypoxia-inducible factor-1α; membrane-type 2 matrix metalloproteinase; pancreatic cancer; prognosis; tumor progression