Molecular mechanisms of cancer cell progression during liver metastasis formation

肝转移形成过程中癌细胞进展的分子机制

基本信息

批准号：
11672162
负责人：
HIGASHI Nobuaki
金额：
$ 2.3万
依托单位：
Graduate School of Pharmaceutical Sciences, The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

The aim of this proposal was to elucidate molecular mechanisms of liver metastasis formation of colon cancer. Our main interest was how host respond during the metastasis process. We have concentrated on the following two research subjects.(1) Adhesion and recognition mechanisms between cancer cells and the liver in the early phase of metastasis : Expression of FH6 monoclonal Ab determinant on colon carcinoma correlates malignancy of the tumor. A colon carcinoma cell line KM 12 expresses FH6 determinant, a unique carbohydrate structure on the following points, containing sialylation anfd fucosylation, not recognized by a part of anti-sialyl lewis X Abs, sensitive to endo-β-glycosidase digestion. To elucidate molecular properties of the carbohydrates we artificially reconsituted FH6 determinants by FUT6 gene transfection into KM 12-LX that lacks expression of FH6 determinant. We showed that hepatocytes recognized the FH6 determinant in the liver. We are now determining the structure of … More 49 kD protein as a candidate of the recognition molecule.(2) Established liver metastasis formation accompanied with reconstitution of host tissues around micrometastasis : We have established a mouse experimental metastasis model that reproduces reconstitution of host tissue around micrometastasis and formation of established metastasis. Based on histochemical observations, we have classified the formation of established metastasis into three steps ; micrometastasis, transient micrometastasis, and established metastasis. In micrometastasis, paticular host cells infilrated into the matastasis region. In transient micrometastasis, many types of host cells infiltrated. Fibroblastic tissue protrusion appeared that accompanied with extracellular matrices and neovascularization and linked neighboring micrometastases. We believe that the process is important as an initial event of fibrosis formation. Established metastasis was rich in fibroblastic stromal tissue. Colon 38 cells separately distributed from host cells in the stromal tissue. We postulate a certain mechanism to separate cancer and stroma in the process of established metasiasis formation. Less

结肠癌的肝脏转移的分子机制，我们集中于以下两个研究对象。 OMA细胞系KM 12表达FH6的决定因素，这是一种独特的碳水化合物结构，在以下几点中，降低了Anfd Fucothisos，而不是由抗siaLyl Lewis X ABS的一部分识别为内部β-糖苷酶的一部分。 Determinants by Fut6 Gene Transfection Into KM 12-Lacks Lacks Expression of FH6 Determinant. We Showed that Hepatocytes Recognant The FH6 Determinant in The Liver. ITABLISHED LIVER METASTASIS FORMATION With Reconstation of Host Tissues Around Micrometastastastastastastastastastastastastastastastastastastasis: we have Established a MOUSE EXPRODUDUCES MODEL MODEL MODEL TISTUE在基于ED的转移的情况下，我们将已建立的转移分为三个步骤；邻近的微晶和纤维形成的初始事件很重要。