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Futagami S Tatsuguchi A Hiratsuka T Shindo T Horie A Hamamoto T Ueki N Kusunoki M Miyake K Gudis K Tsukui T Sakamoto C 《Journal of gastroenterology》2008,43(3):216-224
Background Recent studies have reported that expression of monocyte chemoattractant protein 1 (MCP-1) and its receptor (CCR2) and CD40
ligation on mesenchymal cells play important roles in tumor development. Cyclooxygenase 2 (COX-2) has also been shown to contribute
to tumor angiogenesis. We examined the interaction between MCP-1 and CD40 ligation in mesenchymal cells in gastric cancer
to determine the effect of these factors on vascular endothelial growth factor (VEGF) production via upregulation of COX-2
expression.
Methods COX-2, prostaglandin E2 (PGE2), and VEGF production were evaluated in CD40 ligand (CD40L)-stimulated macrophages. CD40L and MCP-1 mRNA levels in gastric
cancer tissues were evaluated by real-time polymerase chain reaction (PCR). Localizations of MCP-1, CD40L, CD34, CD40, and
CCR2 in 34 gastric cancer tissue specimens were evaluated by single-or double-label immunohistochemistry.
Results COX-2 expression levels were significantly higher in CD40L-stimulated macrophages and correlated with increased PGE2 and VEGF production. Addition of MCP-1 to CD40L-stimulated macrophages had a synergistic effect on COX-2 expression and subsequent
PGE2 and VEGF production. CD40L and MCP-1 mRNA levels were significantly higher in poorly differentiated gastric cancers than
in H. pylori-infected gastritis patients. High microvessel density was significantly associated with MCP-1 and CCR2 scores and lymph node
metastasis.
Conclusions MCP-1 and CD40L had a synergistic effect on COX-2 expression and subsequent VEGF production in gastric cancer. 相似文献