A distinctive set of genes is upregulated during the inflammation-carcinoma sequence in mouse stomach infected by Helicobacter felis.
Helicobacter pylori infects over half the population worldwide and is a leading cause of chronic gastritis and gastric cancer. However, the mechanism by which this organism induces inflammation and carcinogenesis is not fully understood. In the present study we used insulin-gastrin (INS-GAS) transgenic mice that fully develop gastric adenocarcinoma after infection of H. pylori-related Helicobacter felis. Histological examination revealed that more than half of those mice developed invasive adenocarcinoma after 8 months of infection. These carcinomas were stained by NCC-ST-439 and HECA-452 that recognize 6-sulfated and non-sulfated sialyl Lewis X. Lymphocytic infiltration predominantly to submucosa was observed in most H. felis-infected mice, and this was associated with the formation of peripheral lymph node addressin (PNAd) on high endothelial venule (HEV)-like vessels detected by MECA-79. Time-course analysis of gene expression by using gene microarray revealed upregulation of several inflammation-associated genes including chemokines, adhesion molecules, surfactant protein D (SP-D), and CD74 in the infected stomach. Immunohistochemical analysis demonstrated that SP-D is expressed in hyperplasia and adenocarcinoma whereas CD74 is expressed in adenocarcinoma in situ and invasive carcinoma. These results as a whole indicate that H. felis induces HEV-like vessels and inflammation-associated chemokines and chemokine receptors, followed by adenocarcinoma formation.
Kobayashi
Motohiro
M
Glycobiology Program, Cancer Research Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Lee
Heeseob
H
Schaffer
Lana
L
Gilmartin
Tim J
TJ
Head
Steven R
SR
Takaishi
Shigeo
S
Wang
Timothy C
TC
Nakayama
Jun
J
Fukuda
Minoru
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D005755:Gastrins / Q000235:genetics; D005756:Gastritis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D016695:Glycosyltransferases / Q000096:biosynthesis / Q000235:genetics; D016481:Helicobacter Infections / Q000378:metabolism*; D044922:Helicobacter felis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006965:Hyperplasia; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D009844:Oligosaccharides / Q000096:biosynthesis; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis; D000080506:Sialyl Lewis X Antigen; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015854:Up-Regulation
D000944:Antigens, Differentiation, B-Lymphocyte; D005755:Gastrins; D000949:Histocompatibility Antigens Class II; D007328:Insulin; D009844:Oligosaccharides; D037663:Pulmonary Surfactant-Associated Protein D; D000080506:Sialyl Lewis X Antigen; C045084:invariant chain; D016695:Glycosyltransferases