| Project/Area Number |
11672162
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | Graduate School of Pharmaceutical Sciences, The University of Tokyo |
|---|
Principal Investigator |
HIGASHI Nobuaki Graduate School of Pharmaceutical Sciences, The University of Tokyo, 大学院・薬学系研究科, 講師 (40302616)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IRIMURA Tatsuro Graduate School of Pharmaceutical Sciences, The University of Tokyo, 大学院・薬学系研究科, 教授 (80092146)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | Liver metastasis / Colon Carcinoma / Carbohydrate tumor antigen / Sialyl Lewis X / Fibrosis / Angiogenesis / Fibroblasts / Stromal tissue / 癌転移 / 癌と宿主の相互作用 / 線維芽細胞 / マクロファージ / 血管内皮細胞 / 接着分子 |
|---|
| Research Abstract |
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
|
