Monocyte chemoattractant protein-1 is generated via TGF-beta by myofibroblasts in gastric intestinal metaplasia and carcinoma without H. pylori infection.

Abstract

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-beta1 (TGF-beta1) mRNA expression levels and single- or double-label immunohistochemistry was used to evaluate the localization of MCP-1, TGF-beta type I receptor, and alpha-smooth muscle actin (alphaSMA). 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-beta type I receptor were co-expressed in the alphaSMA-positive myofibroblasts of intestinal metaplastic mucosa and gastric carcinoma. Exogenous application of TGF-beta1 increased MCP-1 mRNA expression levels in the intestinal metaplastic tissue. Furthermore, TGF-beta1 was overexpressed and macrophage was strongly infiltrated in the gastric carcinoma. In conclusion, MCP-1 expression, which was stimulated by TGF-beta1, was recognized in the TGF-beta 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.

• Authors: Hiroyuki Mutoh, Miho Sashikawa, Hiroko Hayakawa, Kentaro Sugano
• Journal: Cancer science (Cancer Sci) Vol. 101 Issue 8 Pg. 1783-9 (Aug 2010) ISSN: 1349-7006 [Electronic] England
• PMID: 20557309 (Publication Type: Journal Article)

Chemical References

• Actins
• CDX2 Transcription Factor
• Ccl2 protein, mouse
• Cdx2 protein, mouse
• Chemokine CCL2
• Homeodomain Proteins
• Receptors, Transforming Growth Factor beta
• Transcription Factors
• Transforming Growth Factor beta1
• alpha-smooth muscle actin, mouse
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type I

Topics

• Actins (analysis)
• Animals
• CDX2 Transcription Factor
• Chemokine CCL2 (analysis, biosynthesis)
• Female
• Fibroblasts (metabolism)
• Gastric Mucosa (pathology)
• Helicobacter Infections (complications)
• Helicobacter pylori
• Homeodomain Proteins (physiology)
• Immunohistochemistry
• Macrophages (physiology)
• Male
• Metaplasia
• Mice
• Mice, Transgenic
• Protein Serine-Threonine Kinases (analysis)
• Receptor, Transforming Growth Factor-beta Type I
• Receptors, Transforming Growth Factor beta (analysis)
• Stomach Neoplasms (metabolism)
• Transcription Factors (physiology)
• Transforming Growth Factor beta1 (physiology)