title: Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer.
abstract: Helicobacter pylori is an important pathogenic factor in gastric carcinogenesis. Angiogenesis (i.e., the growth of new blood vessels) is closely associated with the incidence and development of gastric cancer. Our previous study found that COX-2 stimulates gastric cancer cells to induce expression of the angiogenic growth factor VEGF through an unknown mechanism. Therefore, the aim of this study was to clarify the role of angiogenesis in H. pylori-induced gastric cancer development.
  
  
  
  To clarify the relationship between H. pylori infection and angiogenesis, we first investigated H. pylori colonization, COX-2, VEGF, beta-catenin expression, and microvessel density (MVD) in gastric cancer tissues from 106 patients. In addition, COX-2, phospho-beta-catenin, and beta-catenin expression were measured by western blotting, and VEGF expression was measured by ELISA in H. pylori-infected SGC7901 and MKN45 human gastric cancer cells.
  
  
  
  H. pylori colonization occurred in 36.8 % of gastric carcinoma samples. Furthermore, COX-2, beta-catenin, and VEGF expression, and MVD were significantly higher in H. pylori-positive gastric cancer tissues than in H. pylori-negative gastric cancer tissues (P < 0.01). H. pylori infection was not related to sex or age in gastric cancer patients, but correlated with the depth of tumor invasion, lymph node metastasis, and tumor-node-metastasis stage (P < 0.05) and correlated with the COX-2 expression and beta-catenin expression(P < 0.01). Further cell experiments confirmed that H. pylori infection upregulated VEGF in vitro. Further analysis revealed that H. pylori-induced VEGF expression was mediated by COX-2 via activation of the Wnt/beta-catenin pathway.
  
  
  
  The COX-2/Wnt/beta-catenin/VEGF pathway plays an important role in H. pylori-associated gastric cancer development. The COX-2/Wnt/beta-catenin pathway is therefore a novel therapeutic target for H. pylori-associated gastric cancers.
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
authors.forename: Ni
authors.initials: N
authors.lastname: Chai
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
authors.forename: Haili
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China. Lzwf@hotmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
mesh_terms: D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000382:microbiology*; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000382:microbiology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Angiogenesis; Cyclooxygenase 2; Gastric cancer; Helicobacter pylori; Vascular endothelial growth factor; Wnt/beta-catenin