| Project/Area Number |
07671821
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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 |
Obstetrics and gynecology
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| Research Institution | Keio University |
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Principal Investigator |
TSUKAZAKI Katsumi Keio Univ.Sch.of Med.Assistant Professor, 医学部, 講師 (40118972)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | endometrial cancer / glycosyltransferase / vascular endothelium / 体癌細胞 / H_1型糖鎖 / H_2糖鎖 / 複合糖質 / 発現異常 / 糖転移酵素 / モノクローナル抗体 / 転移 |
|---|
| Research Abstract |
The present study was conducted to (1) analyze quantitative and qualitative changes in fucosyltransferase (FT) occurring after malignant transformation of endometrial cells and (2) elucidate the role of fucosylated carbohydrate chains in endometrial cancer cell metastasis.
1. Cultured endometrial cancer SNG-II cells were divided into two sublines based on expression of Lewis^b-type carbohydrate chains (Le^b) : (a) SNG-S cells which strongly express Le^b and exhibit increased activity of alpha1-4FT (FTIII), which is involved in the synthesis of Le^b, and (b) SNG-W cells with no Le^b and decreased FTIII activity. Investigation of the expression of FTIII mRNA in SNG-II,SNG-S,and SNG-W cells using the Northern blot transfer technique with FTIII cDNA showed that only SNG-II and SNG-S express FTIII mRNA.These results indicate that the rise in glycosyltransferase activity responsible for abnormal carbohydrate chain expression following malignant change is partly attributable to an increase in
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glycosyltransferase protein levels caused by increased expression of glycosyltransferase mRNA.
2. The ability of SNG-S and SNG-W cells to adhere to human umbilical vein endothelial cells (HUVEC) and the capacity of antibodies to inhibit such adhesion were evaluated using in situ adhesion assay. The adhesiveness to HUVEC of SNG-W cells, which do not express Le^b molecules but do express their precursor H_1-type carbohydrate chains (H_1), was approximately double that of SNG-S cells. Adhesion of SNG-W cells to HUVEC was inhibited by anti-H_1 antibody in a dose-dependent manner. When SNG-W cells with high metastatic ability were injected into the tail vein of nude mice treated with anti-H_1 or anti-H_2 antibody, 36.7% of the animals treated with anti-H_2 antibody developed pulmonary metastasis after 8 weeks versus 13.3% of those treated with anti-H_2 antibody. These findings show that H_1 plays an important role in the ability of SNG-W cells to adhere to blood vessels and to metastasize distantly. The ligand for H_1 on the vascular endothelium was sought using H_1 beads. Adhesion of H_1 beads to endometrial cells increased 6-fold when the cells were pretreated with IL-1beta, suggesting that the ligand for H_1 on the vascular endothelium is an adhesion molecule whose expression is increased by treatment with IL-1beta. Less
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