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

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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.