2002 Fiscal Year Final Research Report Summary
REGULATION OF ANGIOGENESIS BY INFLAMATORY CYTOKINES IN HUMAN GASTRIC CARCINOMAS
| Project/Area Number |
12670488
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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 | HIROSIMA UNIVERSITY |
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Principal Investigator |
KITADAI yasuhiko Hiroshima University Medical Hospital, Assistant Professor, 医学部附属病院, 講師 (10304437)
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| Co-Investigator(Kenkyū-buntansha) |
HARUMA ken Department of Internal Medicine, Kawasaki Medical School, Professor, 内科学消化器II, 教授 (40156526)
YOSHIHARA masaharu Health Service Center, Professor, 保健管理センター, 教授 (20211659)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Gastric Cancer / Angiogenesis / Cytokine / IL-8 / VEGF / MCP-1 / Macrophage |
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| Research Abstract |
1.We have previously reported that expression of interleukin (IL)-8 by human gastric carcinomas directly correlates with tumor vascularity. To determine whether IL-8 can act in an autocrine manner to regulate the expression of disease-progression genes, we examined the expression of IL-8 receptors in human gastric carcinomas. All of the gastric carcinoma cell lines expressed mRNA and protein for IL-8 receptors. In vitro treatment of human gastric cancer MKN-1 cells with exogenous IL-8 enhanced the expression of EGFR, MMP-9, and VEGF mRNA. IL-8 may play a role in the progressive growth of human gastric carcinoma by autocrine / paracrine mechanisms.
2. Next, we examined whether IL-8 and VEGF co-expression correlates with clinicopathological parameters in human gastric carcinoma. IL-8 level in the neoplasms correlated significantly with depth of invasion, venous invasion, and lymphatic invasion. VEGF expression in tumors correlated well with depth of invasion and lymph node metastasis. Sur
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vival rate of patients with tumors displaying high IL-8 and VEGF expression levels was significantly lower than that of patients with tumors displaying low IL-8 and VEGF expression. IL-8 and VEGF together promote tumors by stimulating angiogenesis in human gastric carcinoma.
3.The role of interactions between tumor cells and macrophages in angiogenesis of human gastric carcinomas was investigated. Macrophage infiltration in tumors and monocyte chemoattractant protein-1 (MCP-1) expression were examined in 72 archival specimens of gastric carcinoma with reference to tumor vascularity. MCP-1 expression in tumor cells increased with the depth of tumor invasion, this also being the case for microvessel density and macrophage infiltration. Macrophage counts were well correlated with vessel counts and those were significantly higher in the MCP-1 positive than in the negative tumors. MCP-1 produced by tumor cells may play a role in angiogenesis via macrophage recruitment and activation in human gastric carcinoma. Less
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