Matrix Metalloproteinase 11 as a Novel Tumor Promoter and Diagnostic and Prognostic Biomarker for Pancreatic Ductal Adenocarcinoma

Pancreas. 2020 Jul;49(6):812-821. doi: 10.1097/MPA.0000000000001583.

Abstract

Objectives: Matrix metalloproteinase 11 (MMP-11) was found to be implicated in tumorigenesis in cancers. However, the significance of MMP-11 in pancreatic ductal adenocarcinoma (PDAC) is unclear.

Methods: In the study, we detected malignant biological behaviors of pancreatic cancer after downregulation of MMP-11. Furthermore, we explored the possible mechanism, and the diagnostic value of serum MMP-11 level was analyzed in 116 patients with pathologically confirmed PDAC. In addition, we explored their prognostic value in PDAC.

Results: We observed that MMP-11 could be expressed and activated in the cytoplasm of PDAC cells. Immunohistochemistry staining of PDAC tissues showed that MMP-11 was highly expressed in cancerous ductal epithelium instead of cancer stroma. We found that downregulation of MMP-11 inhibited proliferation of PDAC cell lines. The expression levels of cyclin-dependent kinase 4 and cyclin D1 were downregulated after MMP-11 knockdown. As for its clinical value, the serum level of MMP-11 was shown to be a potent promising diagnostic marker for PDAC.

Conclusions: Matrix metalloproteinase 11 may act as a tumor promoter, playing a positive role in PDAC development. Serum MMP-11 also has great potential to be a promising diagnostic marker for PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinogens*
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / enzymology
  • Carcinoma, Pancreatic Ductal / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Matrix Metalloproteinase 11 / blood
  • Matrix Metalloproteinase 11 / genetics*
  • Matrix Metalloproteinase 11 / metabolism
  • Middle Aged
  • Pancreas / enzymology
  • Pancreas / metabolism
  • Pancreas / pathology
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / genetics*
  • Prognosis
  • RNA Interference

Substances

  • Biomarkers, Tumor
  • Carcinogens
  • Matrix Metalloproteinase 11