title: Autoimmune gastritis mediated by CD4+ T cells promotes the development of gastric cancer.
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.
authors: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
authors: Thanh-Long M
authors: TL
authors: Nguyen
authors: Shradha S
authors: SS
authors: Khurana
authors: Clifford J
authors: CJ
authors: Bellone
authors: Benjamin J
authors: BJ
authors: Capoccia
authors: John E
authors: JE
authors: Sagartz
authors: Russell A
authors: RA
authors: Kesman
authors: Jason C
authors: JC
authors: Mills
authors: Richard J
authors: RJ
authors: DiPaolo
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008679:Metaplasia / Q000150:complications / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D017506:H(+)-K(+)-Exchanging ATPase
references: J Immunol. 1996 Jun 15;156(12):4729-38
references: 8648119
references: Am J Gastroenterol. 2009 Jun;104(6):1342-5
references: 19491846
references: Gastroenterology. 2010 Jun;138(7):2207-10, 2210.e1
references: 20450866
references: Gastroenterology. 1998 Aug;115(2):340-7
references: 9679039
references: Cancer Res. 1988 Jul 1;48(13):3554-60
references: 3288329
references: Gastroenterology. 2012 Jan;142(1):21-24.e7
references: 22001866
references: Gut. 1990 Oct;31(10):1105-9
references: 2083855
references: Gastroenterology. 1996 Jan;110(1):155-66
references: 8536852
references: Eur J Immunol. 2001 Jul;31(7):2094-103
references: 11449363
references: Diabetes. 1982 Dec;31(12):1051-5
references: 7173496
references: Am J Pathol. 2010 Sep;177(3):1514-33
references: 20709804
references: Ann Oncol. 2012 Aug;23(8):2179-2184
references: 22228448
references: Science. 1996 Oct 11;274(5285):259-62
references: 8824193
references: Development. 2007 Jan;134(1):211-22
references: 17164426
references: J Exp Med. 2003 Oct 20;198(8):1147-56
references: 14568977
references: J Clin Endocrinol Metab. 1999 Nov;84(11):4062-7
references: 10566650
references: Gastroenterology. 1985 Mar;88(3):638-48
references: 2578420
references: Autoimmunity. 1993;16(4):289-95
references: 7517707
references: Scand J Gastroenterol. 2002 Mar;37(3):287-93
references: 11916190
references: J Immunol. 2000 Jul 15;165(2):1022-9
references: 10878379
references: Gastroenterology. 2005 May;128(6):1717-51
references: 15887161
references: J Mol Med (Berl). 2012 Sep;90(9):1037-46
references: 22328012
references: JAMA. 2004 Jan 14;291(2):187-94
references: 14722144
references: Oncogene. 2000 Apr 6;19(15):1868-74
references: 10773876
references: Gastroenterology. 2000 Jan;118(1):36-47
references: 10611152
references: Am J Physiol Gastrointest Liver Physiol. 2007 Jan;292(1):G1-5
references: 16935852
references: J Immunol. 2005 Dec 1;175(11):7135-42
references: 16301616
references: Clin Cancer Res. 2005 Feb 15;11(4):1386-93
references: 15746037
references: Lancet. 1970 Jul 25;2(7665):163-8
references: 4193564
references: J Leukoc Biol. 2010 Dec;88(6):1145-56
references: 20610800
references: Cancer. 2011 Mar 15;117(6):1163-71
references: 21381009
references: J Clin Invest. 2008 Jul;118(7):2459-70
references: 18535670
references: Gastroenterology. 2008 Feb;134(2):511-22
references: 18242217
references: Clin Immunol Immunopathol. 1997 Sep;84(3):223-43
references: 9281381
references: J Pathol. 2007 Oct;213(2):140-51
references: 17724739
references: J Immunol. 2010 May 1;184(9):5121-9
references: 20351183
references: Gastroenterology. 2004 Jan;126(1):196-207
references: 14699500
references: Autoimmunity. 1995;21(3):215-21
references: 8822279
references: Scand J Gastroenterol. 1998 Jan;33(1):88-92
references: 9489914
references: Br J Cancer. 1989 May;59(5):810-3
references: 2736218
references: Am J Physiol Gastrointest Liver Physiol. 2006 May;290(5):G970-9
references: 16399875
references: Cancer Res. 2005 Dec 1;65(23):10709-15
references: 16322215
references: Arch Intern Med. 1996 May 27;156(10):1097-100
references: 8638997
references: Int Rev Immunol. 2005 Jan-Apr;24(1-2):111-22
references: 15763992
references: Int J Cancer. 2009 Nov 15;125(10):2383-92
references: 19670418
references: Cancer. 1993 Feb 1;71(3):745-50
references: 8431855
references: Arch Intern Med. 1999 Aug 9-23;159(15):1726-30
references: 10448775