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.
©2013 AACR.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / etiology
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Animals
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Autoimmune Diseases / etiology*
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Autoimmune Diseases / metabolism
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Autoimmune Diseases / pathology
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Blotting, Western
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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Flow Cytometry
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Fluorescent Antibody Technique
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Gastric Mucosa / immunology
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Gastric Mucosa / metabolism
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Gastric Mucosa / pathology
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Gastritis / complications*
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Gastritis / immunology
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Gastritis / pathology
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H(+)-K(+)-Exchanging ATPase / immunology*
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Humans
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Immunoenzyme Techniques
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Inflammation / complications*
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Inflammation / immunology
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Inflammation / pathology
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Interferon-gamma / metabolism
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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Metaplasia / complications
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Metaplasia / immunology
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Metaplasia / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Receptors, Antigen, T-Cell / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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Stomach Neoplasms / etiology*
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Stomach Neoplasms / metabolism
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Stomach Neoplasms / pathology
Substances
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RNA, Messenger
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Receptors, Antigen, T-Cell
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Interferon-gamma
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H(+)-K(+)-Exchanging ATPase