Human gastric cancer development with TNF-α-inducing protein secreted from Helicobacter pylori

TNF-α-inducing protein (Tipα) is a unique carcinogenic factor of Helicobacter pylori, which is secreted into culture broth. The biological activities of Tipα and deletion mutant were studied. Tipα protein specifically binds to cell-surface nucleolin and then enters the gastric cancer cells, where TNF-α and chemokine gene expressions are induced by NF-κB activation. Nucleolin localizes on the surface of gastric cancer cells, and interaction between Tipα and cell-surface nucleolin causes a cancer-oriented microenvironment that increases the risk of gastric cancer. This paper discusses a new mechanism of gastric cancer development with H. pylori and provides a new preventive strategy.