TY - JOUR
T1 - Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer
AU - Nguyen, Thanh Long M.
AU - Khurana, Shradha S.
AU - Bellone, Clifford J.
AU - Capoccia, Benjamin J.
AU - Sagartz, John E.
AU - Kesman, Russell A.
AU - Mills, Jason C.
AU - DiPaolo, Richard J.
PY - 2013/4/1
Y1 - 2013/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84876005485&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-12-3957
DO - 10.1158/0008-5472.CAN-12-3957
M3 - Article
C2 - 23378345
AN - SCOPUS:84876005485
SN - 0008-5472
VL - 73
SP - 2117
EP - 2126
JO - Cancer research
JF - Cancer research
IS - 7
ER -