CD44 Plays a Functional Role in -induced Epithelial Cell Proliferation

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Chronic gastric inflammation, typically caused by Helicobacter pylori (H. pylori), is the most consistent lesion leading to cancer. During a well-choreographed interaction between H. pylori and the host, the progression from chronic inflammation to cancer involves gastric epithelial changes with evidence of hyperproliferation. Our knowledge of H. pylori pathogenesis is predominantly based on data generated from gastric cancer cell lines or animal models of inflammation. We report the development and use of a novel model of primary human and mouse cultured gastric epithelial cells that are organized into three-dimensional spheroid units containing a lumen, known as gastric organoids. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the bacteria. Cluster-of-differentiation gene (CD44) is a transmembrane receptor responsible for epithelial cell proliferation. We show that CD44 plays a functional role in H. pylori-induced proliferation. In a Mongolian gerbil animal model of H. pylori-induced gastric cancer, we show that inhibiting CD44 blocks epithelial proliferation and subsequently cancer progression in response to bacterial infection. Thus our study provides new insights into the role of CD44 in H. pylori-induced hyperproliferation and progression of gastric disease.

Vyšlo v časopise: CD44 Plays a Functional Role in -induced Epithelial Cell Proliferation. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004663
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004663

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