Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer

Thanh Long M. Nguyen, Shradha S. Khurana, Clifford J. Bellone, Benjamin J. Capoccia, John E. Sagartz, Russell A. Kesman, Jason C. Mills, Richard J. DiPaolo

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Chronic inflammation is a major risk factor for cancer, including gastric cancers and other gastrointestinal cancers. For example, chronic inflammation caused by autoimmune gastritis (AIG) is associated with an increased risk of gastric polyps, gastric carcinoid tumors, and possibly adenocarcinomas. In this study, we characterized the progression of gastric cancer in a novel mouse model of AIG. In this model, disease was caused by CD4+ T cells expressing a transgenic T-cell receptor specific for a peptide from the H +/K+ ATPase proton pump, a protein expressed by parietal cells in the stomach. AIG caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancers, including chronic gastritis followed by oxyntic atrophy, mucous neck cell hyperplasia, spasmolytic polypeptide-expressing metaplasia, dysplasia, and ultimately gastric intraepithelial neoplasias. Our work provides the first direct evidence that AIG supports the development of gastric neoplasia and provides a useful model to study how inflammation drives gastric cancer.

Original languageEnglish
Pages (from-to)2117-2126
Number of pages10
JournalCancer research
Volume73
Issue number7
DOIs
StatePublished - Apr 1 2013

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