Open AccessMonocyte chemoattractant protein‐1 is generated via TGF‐β by myofibroblasts in gastric intestinal metaplasia and carcinoma without H. pylori infection
Author(s) -
Mutoh Hiroyuki,
Sashikawa Miho,
Hayakawa Hiroko,
Sugano Kentaro
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01609.x
Subject(s) - intestinal metaplasia , cdx2 , gastric mucosa , stomach , biology , immunohistochemistry , pathology , monocyte , helicobacter pylori , metaplasia , cancer research , medicine , immunology , gene expression , biochemistry , homeobox , gene
Helicobacter pylori ( H. pylori ) stimulates secretion of monocyte chemoattractant protein 1 (MCP‐1) from gastric mucosa. Monocyte chemoattractant protein‐1 (MCP‐1) expression and macrophage infiltration are recognized in human gastric carcinoma. We have previously generated Cdx2‐transgenic mice as model mice for intestinal metaplasia. Both chronic H. pylori ‐associated gastritis and Cdx2‐transgenic mouse stomach develop intestinal metaplasia and finally gastric carcinoma. In this study we have directed our attention to MCP‐1 expression in the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2‐transgenic mouse stomach. Quantitative real‐time PCR was performed to determine MCP‐1 and transforming growth factor ‐β1 ( TGF‐β1 ) mRNA expression levels and single‐ or double‐label immunohistochemistry was used to evaluate the localization of MCP‐1, TGF‐β type I receptor, and α‐smooth muscle actin (αSMA). We determined that MCP‐1 mRNA dramatically increased in the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2‐transgenic mouse stomach, compared with normal mouse stomach. Both MCP‐1 and TGF‐β type I receptor were co‐expressed in the αSMA‐positive myofibroblasts of intestinal metaplastic mucosa and gastric carcinoma. Exogenous application of TGF‐β1 increased MCP‐1 mRNA expression levels in the intestinal metaplastic tissue. Furthermore, TGF‐β1 was overexpressed and macrophage was strongly infiltrated in the gastric carcinoma. In conclusion, MCP‐1 expression, which was stimulated by TGF‐β1, was recognized in the TGF‐β type I receptor‐expressing myofibroblasts of the intestinal metaplastic mucosa and the gastric carcinoma of Cdx2‐transgenic mouse stomach. The present results suggest that intestinal metaplasia and gastric carcinoma themselves induce MCP‐1 expression independently of H. pylori infection. ( Cancer Sci 2010)