Helicobacter pylori strain-selective induction of matrix metalloproteinase-7 in vitro and within gastric mucosa

Gastroenterology. 2003 Oct;125(4):1125-36. doi: 10.1016/s0016-5085(03)01206-x.


Background and aims: Helicobacter pylori strains that possess the cag pathogenicity island (cag(+)) augment the risk for distal gastric cancer. Matrix metalloproteinase (MMP)-7, an epithelial cell-derived MMP that is induced by bacterial contact, is overexpressed within human gastric adenocarcinoma specimens and enhances tumor formation in rodents. We determined whether H. pylori alters MMP-7 expression and investigated the molecular pathways required for these events.

Methods: MMP-7 was detected in human gastric mucosa by immunohistochemistry and in H. pylori/AGS gastric epithelial cell coculture supernatants by Western analysis. AGS cells were cocultured with wild-type H. pylori, or isogenic cagA(-), cagE(-), or vacA(-) mutants, in the absence or presence of inhibitors of nuclear factor kappaB activation, p38, or extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase.

Results: H. pylori cag(+) strains increased MMP-7 expression in AGS cells 5-7-fold, whereas cag(-) isolates had no effect. Inactivation of cagE, but not cagA or vacA, completely attenuated induction of MMP-7, and inhibition of ERK 1/2 decreased MMP-7 production. In vivo, MMP-7 was expressed in gastric epithelial cells in specimens from 80% of cag(+)-colonized persons but in none of the cag(-) or uninfected subjects.

Conclusions: H. pylori cag(+) strains enhance levels of MMP-7 within inflamed mucosa. In vitro, cag(+) isolates selectively induce MMP-7, and this is dependent on activation of ERK 1/2 by specific components within the cag island. Differential induction of MMP-7 by H. pylori cag(+) isolates may explain in part the augmentation in gastric cancer risk associated with these strains.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Gastric Mucosa / cytology
  • Gastric Mucosa / enzymology
  • Gastric Mucosa / microbiology*
  • Helicobacter Infections / metabolism*
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / classification
  • Helicobacter pylori / enzymology*
  • Humans
  • In Vitro Techniques
  • Matrix Metalloproteinase 7 / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Serine Endopeptidases / metabolism
  • Species Specificity
  • Stomach Neoplasms / microbiology
  • Up-Regulation


  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Serine Endopeptidases
  • chymostatin-sensitive angiotensin II-generating enzyme
  • Matrix Metalloproteinase 7