Involvement of tumor necrosis factor-α in the upregulation of CXCR4 expression in gastric cancer induced by Helicobacter pylori

BMC Cancer

Research Article

Xianmin Bu¹  Wei Wang²  Chenghai Zhao²  Xiaomei Lu²  Ning Zhang² 

[1] Department of General Surgery, Shengjing Hospital, China Medical University, Shenyang, China;Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, China;

关键词: Gastric Cancer;    Infliximab;    Pylorus Infection;    Gastric Cancer Cell;    CXCR4 Expression;   

DOI  :  10.1186/1471-2407-10-419

 received in 2009-10-28, accepted in 2010-08-11,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundH. pylori, whose infection increases tumor invasiveness and metastasis, is generally labelled as the strongest risk factor for the development of gastric cancer. It appears not to be a coincidence that there is also an overexpression of CXCR4 and an obvious involvement in gastric cancer metastasis. The aim of this study attempts to investigate and further to establish a link between them. With H. pylori being a potent inducer of TNF-α, whether TNF-α, a tumor promoter, is involved in the induction of CXCR4 expression by H. pylori was also under research in this study.MethodsExpression of CXCR4, TNF-α, IL-6 and IL-1β mRNA was determined by real-time PCR. CXCR4 protein expression was detected by Western blotting. Concentrations of TNF-α, IL-6 and IL-1β in cell culture supernatants were measured using the Quantikine Elisa kit. To abrogate TNF-α expression in HGC27 cells, TNF-α RNAi plasmid was used to transfect them.ResultsLevels of CXCR4 and TNF-α mRNA were significantly higher in H. pylori-positive gastric cancers (n = 19) compared to H. pylori-negative ones (n = 15). A subsequently Spearman's rank correlation test showed there was a positive correlation between the level of CXCR4 mRNA and that of TNF-α in 34 primary gastric cancers. Other results followed: Expression of CXCR4 and TNF-α was upregulated in gastric cancer cell MKN45 and HGC27 after infection with H. pylori 26695 (cag PAI+ ) or Tx30a (cag PAI- ); The induction of CXCR4 expression by H. pylori was inhibited significantly by a neutralizing TNF-α antibody, infliximab; CXCR4 expression was upregulated in MKN45 cells after treatment with exogenous TNF-α or co-culture with macrophage, and was downregulated in HGC27 cells after transfection with TNF-α RNAi plasmid. There was a significant increase in the migration of MKN45 cells treated with H. pylori 26695, and a strong inhibition when AMD 3100, a CXCR4 antagonist, or infliximab, was added.ConclusionsOur findings demonstrated that H. pylori upregulates CXCR4 expression in gastric cancer through TNF-α.

【 授权许可】

CC BY   
© Zhao et al; licensee BioMed Central Ltd. 2010