Abstract
The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.
Highlights
Helicobacter pylori is a Gram-negative bacterium that resides in the gastric lumen and is an important human pathogen
This review summarizes a new gene family, tumor necrosis factor-α (TNF-α)-inducing protein, which is secreted by H. pylori and acts as a tumor promoter
Bhas42 cells, induced 33.3% (6/18) tumor development. These results showed that HPMP1 had strong tumorigenicity compared with urease B and that HP-MP1 acts as a tumor promoter and induces human gastric cancer during H. pylori infection (Table 1) [21]
Summary
Helicobacter pylori is a Gram-negative bacterium that resides in the gastric lumen and is an important human pathogen. Bhas cells, induced 33.3% (6/18) tumor development These results showed that HPMP1 had strong tumorigenicity compared with urease B and that HP-MP1 acts as a tumor promoter and induces human gastric cancer during H. pylori infection (Table 1) [21]. Treatment with rTipα protein stimulated tnf-α expression by approximately 26-fold in Bhas 42 cells, and 2.6 μM rTipα induced transformed foci with 18.0 foci/well of Bhas 42 cells (Table 1) This was similar to TPA (1.6 μM), which induces 38.0 foci/well, indicating that Tipα produced by H. pylori acts as a tumor promoter [22]. IL-1β and TNF-α [32] These results suggest that Tipα is a strong inducer of inflammatory cytokines and chemokines in H. pylori and is involved in tumor promotion and progression in the human stomach
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