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

TNF-alpha-inducing protein (Tip alpha) is a unique carcinogenic factor of Helicobacter pylori, which is secreted into culture broth. The biological activities of Tip alpha and deletion mutant were studied. Tip alpha protein specifically binds to cell-surface nucleolin and then enters the gastric cancer cells, where TNF-alpha and chemokine gene expressions are induced by NF-kappa B activation. Nucleolin localizes on the surface of gastric cancer cells, and interaction between Tip alpha 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.