H. pylori-Induced Microenvironment of Chronic Inflammation Promotes Cancer Development

A recent publication explained how infection with the stomach bacteria Heliobacter pylori promotes the development of gastric cancer.

H. pylori are helical-shaped, Gram-negative bacteria that infect various areas of the stomach and duodenum. While peptic ulcers, gastritis, and duodenitis are caused by H. pylori infection, many who are infected with the organism do not show any symptoms of disease. Helicobacter are the only known microorganisms that can thrive in the highly acidic environment of the stomach. Their helical shape is thought to have evolved to penetrate and favor its motility in the mucus gel layer that lines the stomach.

Chronic gastritis induced by H. pylori is the strongest known risk factor for peptic ulceration and distal gastric cancer, and adherence of the bacteria to gastric epithelial cells is critical for induction of inflammation. The most important known H. pylori strain-specific determinant associated with cancer is the cag pathogenicity island, and cag+ strains augment the risk for severe gastritis and gastric cancer. Using in vitro models of bacterial-gastric epithelial cell interactions, researchers from Vanderbilt University (Nashville, TN, USA) have shown that cag island genes are required for pro-inflammatory cytokine release and induction of apoptosis. Recently, they have used global proteomics approaches to identify additional H. pylori products that are related to pathogenesis within the gastric niche. Extending these results into rodent models (Mongolian gerbils and mice) of H. pylori-induced inflammation and carcinogenesis, they have shown that inactivation of such genes attenuates the development gastric injury and cancer.

In the current study, the investigators concentrated on specific protein factors secreted by cag+ H. pylori. One of these, CagE, was found to induce expression of decay-accelerating factor (DAF), a human gastric epithelial cellular receptor for H. pylori and a mediator of the inflammatory response to this pathogen. H. pylori-induced expression of DAF was dependent upon activation of the p38 mitogen-activated protein kinase pathway but not NF-kappa B (nuclear factor-kappa B).

Since DAF acts to remove nearby immune proteins that can kill cells to prevent unwanted immune damage, increased DAF activity would provide a degree of protection to H. pylori cells in the area. This would allow the bacteria to maintain an environment of persistent inflammation that could reduce the threshold required for more serious diseases--such as gastric cancer--to develop.

Related Links:
Vanderbilt University