Autoimmune Gastritis Mediated by CD4+ T Cells Promotes the Development of Gastric Cancer
| Autor: | Thanh-Long M. Nguyen, Clifford J. Bellone, Russell A. Kesman, John E. Sagartz, Shradha S. Khurana, Benjamin J. Capoccia, Jason C. Mills, Richard J. DiPaolo |
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| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Pathology medicine.medical_specialty Autoimmune Gastritis Blotting Western Receptors Antigen T-Cell Fluorescent Antibody Technique Chronic gastritis Mice Transgenic Adenocarcinoma Biology Real-Time Polymerase Chain Reaction Article Autoimmune Diseases Immunoenzyme Techniques H(+)-K(+)-Exchanging ATPase Interferon-gamma Mice Stomach Neoplasms Metaplasia medicine Gastric mucosa Animals Humans RNA Messenger Inflammation Mice Inbred BALB C Reverse Transcriptase Polymerase Chain Reaction Stomach digestive oral and skin physiology Cancer Flow Cytometry medicine.disease digestive system diseases medicine.anatomical_structure Oncology Gastric Mucosa Gastric Polyp Gastritis Lymph Nodes medicine.symptom |
| Zdroj: | Cancer Research. 73:2117-2126 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. Cancer Res; 73(7); 2117–26. ©2013 AACR. |
| Databáze: | OpenAIRE |
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