Overexpression of matrix metalloproteinase 11 in human gastric carcinoma and its clinicopathologic significance

Hum Pathol. 2010 May;41(5):686-96. doi: 10.1016/j.humpath.2009.10.010. Epub 2010 Jan 8.

Abstract

Matrix metalloproteinase 11 (stromelysin-3) has recently been reported to play a key role in human tumor progression and poor clinical outcome. The aim of this study was to investigate the significance of matrix metalloproteinase 11 expression in gastric cancer. Using real-time quantitative reverse-transcription polymerase chain reaction analysis and immunohistochemistry, we studied matrix metalloproteinase 11 expression levels in non-malignant gastric tissues and in gastric cancer tissues. The association between matrix metalloproteinase 11 expression levels and tumor stage and grade, as well as metastatic potential, was analyzed. Our results show that matrix metalloproteinase 11 expression was significantly higher in gastric cancer specimens compared with nonmalignant tissues at both transcriptional and protein levels, indicating its positive role in the development of gastric cancer. In addition, increased matrix metalloproteinase 11 expression levels were associated with advanced-stage and high-grade tumors, suggesting its involvement in the progression of gastric cancer. More importantly, increased matrix metalloproteinase 11 expression in gastric cancer specimens was correlated with increased expression of IGF-1, a molecule known to stimulate the proliferation, enhanced survival, and migration of cancer cells. Our results demonstrate that matrix metalloproteinase 11 is a novel factor in the development and progression of gastric cancer and suggest that matrix metalloproteinase 11 is a marker for advanced gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Chi-Square Distribution
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 11 / genetics
  • Matrix Metalloproteinase 11 / metabolism*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Matrix Metalloproteinase 11