2007 Fiscal Year Final Research Report Summary
Investigation of APE-1 regulation induced by gamma/delta T cells in intestinal cells
| Project/Area Number |
17590686
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
FUTAGAMI Seiji Nippon Medical School, Internal Medicine, Division of Gastroenterology, Assistant Professor (50247011)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Choitsu Nippon Medical School, Internal Medicine, Division of Gastroenterology, Professor (30196092)
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| Project Period (FY) |
2005 – 2007
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| Keywords | APE-1 / intestinal metaplasia / Cdx2 / MCP-1 / CD40 / CD4OL / COX-2 |
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| Research Abstract |
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 (CD4OL)-stimulated macrophages. CD4OL and MCP-1 mRNA levels in gastric cancer tissues were evaluated by real-time polymerase chain reaction (PCR). Localizations of MCP-1, CD4OL, 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 CD4OL-stimulated macrophages had a synergistic effect on COX-2 expression and subsequent PGE2 and VEGF production. CD4OL 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 CD4OL had a synergistic effect on COX-2 expression and subsequent VEGF production in gastric cancer.
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