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A basic research for profiles of chemokines which expressed at the connective tissue surrounding gastrointestinal cancer

胃肠道癌周围结缔组织表达趋化因子谱的基础研究

基本信息

批准号：
12470261
负责人：
SATOH Seiji
金额：
$ 3.14万
依托单位：
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

Since the tumor invasion and metastasis are occurred not only by cancer cells, but also by non-tumor cells surrounding them, we notice the connective tissue surrounding the tumor.We notice the factors which expressed by the tumor and surroundings, and analyze the expression of genes and proteins of chemokine and others on the cancer. Hence we notice the expression of CD13 and VEGF-C.We revealed that CD13 is involved in cell motility and angiogenesrs, and over expressed in some of the cancer cell lines and node-positive patients with colon cancer.We investigate the surgical samples and then we analyze the relationship between the expressions of VEGFR-3, the receptor for VEGF-C, on the tumoral vessels and the metastasis. Then, using a clinically relevant mouse model of gastric cancer and colon cancer, we challenged anti-angiogenesis and anti-lymphangiogenesis therapy by systemic administration of antagonistic anti-VEGFR-3 antibody. It's revealed that VEGF-C/VEGFR-3 system plays a important role of tumor metastasis.Moreover, we notice the genes of hepatocellular carcinomas, because of chemokines relate to chronic hepatitis. Then, we identified SIAH1 as tumor suppressor gene, which inactivation correlates with tumor progression in hepatocellular carcinomas.We have identified some of factors which relate to invasion and metastasis ofgastrointestinal cancers and hepatocellular carcinomas.

由于肿瘤的侵袭和转移不仅由癌细胞发生，也由其周围的非肿瘤细胞发生，因此我们注意到肿瘤周围的结缔组织。我们注意到肿瘤和周围环境表达的因素，并分析趋化因子等基因和蛋白在肿瘤中的表达。因此我们注意到CD13和VEGF-C的表达。我们发现CD13参与细胞运动和血管生成，并在一些癌细胞系和结阳性结肠癌患者中过度表达。我们对手术标本进行研究，分析VEGF-C受体VEGFR-3在肿瘤血管上的表达与转移的关系。然后，我们使用临床相关的胃癌和结肠癌小鼠模型，通过全身给药抗vegfr -3抗体来挑战抗血管生成和抗淋巴管生成治疗。提示VEGF-C/VEGFR-3系统在肿瘤转移中起重要作用。此外，我们注意到肝细胞癌的基因，因为趋化因子与慢性肝炎有关。然后，我们发现SIAH1是肿瘤抑制基因，其失活与肝细胞癌的肿瘤进展相关。我们已经确定了一些与胃肠道肿瘤和肝细胞癌的侵袭和转移有关的因素。