Knockdown of MMP11 inhibits proliferation and invasion of gastric cancer cells

Int J Immunopathol Pharmacol. 2013 Apr-Jun;26(2):361-70. doi: 10.1177/039463201302600209.

Abstract

Matrix metalloproteinase 11 (MMP11 or stromelysin-3) has recently been reported to play a crucial role in the development and progression of multiple malignancies. The aim of this study was to investigate the function of MMP11 expression in human gastric adenocarcinoma (GAC). Using immunohistochemistry assay, we studied the expression level of MMP11 in GAC and adjacent non-cancerous tissues (ANCT). The association between MMP11 expression and tumor size and pathological grade, as well as metastatic potential was analyzed. Through small hairpin RNA (shRNA)-mediated MMP11 knockdown in SGC-7901 GAC cells, we observed the changes of the biological behaviors of GAC cells. Our results indicated that the rate of positive expression of MMP11 was higher in GAC tissues than in ANCT (55.0 vs 30.0 percent, P=0.025). MMP11 expression had no association with the factors of age or gender of the GAC patients, or the size, pathological staging and lymph node metastases of the tumors (each P greater than 0.05). Furthermore, MMP11 knockdown inhibited the proliferative activities and invasive potential of SGC-7901 GAC cells with decreased expression of IGF-1, PCNA and VEGF. Taken together, our findings demonstrated that MMP11 expression was increased in GAC tissues, but did not correlate with the clinicopathologic features. Knockdown of MMP11 expression could inhibit the proliferation and invasion of GAC cells probably through down-regulation of the IGF-1 signaling pathway, suggesting that MMP11 might be a potential therapeutic target for the treatment of gastric cancer.

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / secondary
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Knockdown Techniques*
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 11 / genetics
  • Matrix Metalloproteinase 11 / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA Interference
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Transfection
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • IGF1 protein, human
  • Proliferating Cell Nuclear Antigen
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Insulin-Like Growth Factor I
  • MMP11 protein, human
  • Matrix Metalloproteinase 11