Overexpression of membrane‑type 2 matrix metalloproteinase induced by hypoxia‑inducible factor‑1α in pancreatic cancer: Implications for tumor progression and prognosis

Zhu,Shi‑Kai; Zhou,Yu; Cheng,Chao; Zhong,Shan; Wu,Han‑Qing; Wang,Bo; Fan,Ping; Xiong,Jiong‑Xin; Yang,Hong‑Ji; Wu,He‑Shui

doi:10.3892/mco.2014.357

Overexpression of membrane‑type 2 matrix metalloproteinase induced by hypoxia‑inducible factor‑1α in pancreatic cancer: Implications for tumor progression and prognosis

Authors:
- Shi‑Kai Zhu
- Yu Zhou
- Chao Cheng
- Shan Zhong
- Han‑Qing Wu
- Bo Wang
- Ping Fan
- Jiong‑Xin Xiong
- Hong‑Ji Yang
- He‑Shui Wu
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Affiliations: Organ Transplant Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China, Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China, Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: July 23, 2014 https://doi.org/10.3892/mco.2014.357
Pages: 973-981

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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.

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