Expression and activity levels of matrix metalloproteinase-7 and in situ localization of caseinolytic activity in colorectal cancer

Clin Biochem. 2014 Sep;47(13-14):1265-71. doi: 10.1016/j.clinbiochem.2014.06.004. Epub 2014 Jun 13.

Abstract

Objectives: Matrix metalloproteinase-7 is capable of degrading several ECM and non-ECM molecules and contributes to colorectal cancer progression and metastasis. Here, we examined the significance of MMP-7 in colorectal tumors by detecting active and latent MMP-7 levels and localization of its caseinolytic activity.

Design and methods: We investigated expression levels, localization, and proteolytic activity of MMP-7 and local caseinolytic activity in colorectal tumor and paired normal tissues by using real time PCR, casein zymography, immunohistochemistry and in situ casein zymography, respectively. In addition the results were compared with clinicopathological variables.

Results: Real time PCR and immunohistochemistry showed that MMP-7 expressions were higher in colorectal tumor tissues than in normal tissues. Also, mRNA expressions of MMP-7 were positively correlated with tumor and pathological stages and negatively correlated with age. Furthermore, MMP-7 mRNA expression had a sensitivity of 81.3% and a specificity of 81.2% at a cut-off value of 0.0006, making it a potential marker for diagnosis of colorectal cancer. According to casein zymography, pro- and active MMP-7 levels were also elevated in tumor tissues. In addition, we assessed local caseinolytic activity using in situ casein zymography. Increased immunoreactivity of MMP-7 and local caseinolytic activity were found in neoplastic cells but not in stromal cells.

Conclusion: We emphasized the significant role of MMP-7 in diagnosis and progression and/or development of colorectal cancer.

Keywords: Casein zymography; Colorectal cancer; In situ casein zymography; Matrix metalloproteinase-7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Caseins / genetics*
  • Caseins / metabolism*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Matrix Metalloproteinase 7 / genetics*
  • Matrix Metalloproteinase 7 / metabolism*
  • RNA, Messenger / genetics

Substances

  • Caseins
  • RNA, Messenger
  • Matrix Metalloproteinase 7