Abstract 4436: Chronic inflammation and gastric carcinogenesis: the role of CD44 variant expression

Abstract

Abstract CD44 is a marker of tumor-initiating cells in gastric cancer. Recently, we have reported that a CD44 variant (CD44v) interacts with xCT, a glutamate-cystine transporter, and manifests enhanced protection against reactive oxygen species (ROS), contributing to tumor growth and resistance to chemo- or radiotherapy. Although an inflammation related metaplasia and/or dysplasia of gastric epithelium is considered as key events in gastric carcinogenesis, the cause or process of these phenomena is not known. We investigated the relationship between CD44v expression and gastric carcinogenesis, using three lineages of gastric cancer mouse models, K19-Wnt1, K19-C2mE, and K19-Wnt1/C2mE mice. We also used CD44-/- K19-Wnt1/C2mE mice and Helicobacter. felis-infected C57BL/6 mice. Chronic inflammation triggered by Helicobactor infection played a major role in CD44v related gastric carcinogenesis. CD44v expression and nuclear factor-kappa B (NF-κB) activation were promoted by inflammatory cytokines, IL-1α and TNF-α, in gastric cancer cell lines. Thus, CD44v+ tumor cell expansion induced by inflammation via NF-κB pathway might contribute to tumor development. Finally, an xCT inhibitor sulfasalazine treatment significantly suppressed tumor growth in K19-Wnt1/C2mE mice. These findings suggest a significant role of CD44v in inflammation-mediated gastric carcinogenesis via ROS defense. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4436. doi:1538-7445.AM2012-4436