Matrix Metalloproteinase-7 and Premalignant Host Responses in Helicobacter pylori-Infected Mice

Helicobacter pylori-induced gastritis is the strongest singular risk factor for gastric adenocarcinoma. Matrix metalloproteinase-7 (MMP-7) is a proteolytic enzyme that can modify the intestinal microbial replicative niche as well as affect tumorigenesis, and H. pylori stimulates expression of MMP-7 in gastric epithelial cells in vitro. Utilizing a transgenic murine model of H. pylori-mediated injury, our experiments now show that gastric inflammation is increased within the context of MMP-7 deficiency, which involves both Th1- and Th17-mediated pathways. Enhanced gastritis in H. pylori-infected mmp-7(-/-) mice is strongly linked to accelerated epithelial cellular turnover. However, more severe inflammation and heightened proliferation and apoptosis are not dependent on MMP-7-mediated bacterial eradication. Collectively, these studies indicate that H. pylori mediated induction of MMP-7 may serve to protect the gastric mucosa from pathophysiologic processes that promote carcinogenesis. Cancer Res; 70(1); 30-5. (C) 2010 AACR.