The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice. Issue 1 (1st February 2016)

• Record Type: Journal Article
• Authors: Garay, Jone; Piazuelo, M. Blanca; Majumdar, Sumana; Li, Li; Trillo-Tinoco, Jimena; Del Valle, Luis; Schneider, Barbara G.; Delgado, Alberto G.; Wilson, Keith T.; Correa, Pelayo; Zabaleta, Jovanny
• Is Part Of: Cancer letters. Volume 371:Issue 1(2016)
• Page Start: 90
• Page End: 98
• Publication Date: 2016-02-01
• Subjects: Inflammation -- Gastritis -- Gastric cancer -- CD44; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.10.037
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: CD44 expression is significantly increased in individuals whose gastric lesions progressed along the gastric precancerous cascade. CD44 is associated with increased Th1 responses, increased tissue damage and higher counts of Gr1+ cells in the gastric tissues of H. pylori infected mice. We show, for the first time, the association of CD44 expression, Th1 responses, cellular infiltration and tissue damage in H. pylori -induced gastritis. Abstract: Infection with Helicobacter pylori ( H. pylori ) leads to inflammatory events that can promote gastric cancer development. Immune cells transition from the circulation into the infected mucosa through the interaction of their receptors and ligands in the endothelial compartment. CD44 expression is increased in advanced gastric lesions. However, the association of this molecule with the progression of these lesions over time has not been investigated. In addition, there is a lack of understanding of the CD44-dependent cellular processes that lead to gastritis, and possibly to gastric cancer. Here we studied H. pylori -positive subjects with gastric lesions that ranged from multifocal atrophic gastritis to dysplasia to determine gene expression changes associated with disease progression over a period of 6 years. We report that CD44 expression is significantly increased in individuals whose gastric lesions progressed along the gastric precancerous cascade. We also show that CD44−/− mice develop less severe and less extensive H. pylori -induced metaplasia, and show fewer infiltrating Gr1+ cells compared to wild type mice. We present data suggesting that CD44 is associated with disease progression. Mechanisms associated with these effects include induction of interferon gamma responses.