| Co-Investigator(Kenkyū-buntansha) |
KUBUSHIRO Kaneyuki Keio Univ., Sch.of Med., Instructor, 医学部, 助手 (50170022)
AOKI Daisuke Keio Univ., Sch.of Med., Instructor, 医学部, 助手 (30167788)
TSUKAZAKI Katsumi Keio Univ., Sch.of Med., Assistant Professor, 医学部, 講師 (40118972)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1994: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Research Abstract |
We studied the mechanism and biological significance of fucosylated carbohydrate chains expressed in endometrial cancer. We measured fucosyltransferase (FT) activity in two substrains of SNG-II derived from uterine endometrial cancer : SNG-S (a Lewis^b type carbohydrate chain expressing substrain) and SNG-W (an H type carbohydrate chain expressing substrain). Among alpha 1-2FTalpha 1-3FT,alpha 1-4FT activity, only the last was clearly higher in SNG-S than in SNG-W.This indicated that expression of the FTIII gene, which codes for alpha 1-4FT,was stronger in SNG-S than in SNG-W.In order to elucidate the biological significance of Lewis^b type and H type antigen, we studied the cell biological properties of both SNG-S and SNG-W,which have different mechanisms for expressing fucosylated carbohydrate chains as indicated above. When adhesion of these cells to the vascular endothelium was studied in vitro, the number of adherent SNG-W cells was about twice that of SNG-S cells. When in vivo me
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tastasis was studied by injecting the two substrains into the tail veins of nude mice and examining the frequency of lung metastasis, SNG-W showed significantly more lung metastasis than SNG-S.Adhesion of SNG-W to the vascular epithelium was dose-dependently inhibited by and anti-H type carbohydrate chain antibody, but was not inhibited byantibodies fro other blood-group related carbohydrate chains. When SNG-W was treated with the anti-H type carbohydrate chain anitibody and used in the nude mouse lung metastasis model, the frequency of metastasis was lower than in untreated animals. These results indicated that expression of the Lewis^b type and H type carbohydrate chains was involved in biological properties such as adhesion to the vascular epithelium and metastasis of uterine endometrial cancer cells. It was alsosuggested thet uterine endometrial cancer cells which express the H type carbohydrate chain may show a high rate of metastasis.
Galactosyltransferase (GalT) associated with tumor, GAT,which is thought to be the oligomers of GalT derived from healthy individuals, is considerably elevated in sera of ovarian cancer patients. To elucidate why GAT is exclusively released from ovarian cancers, (1) the expression of GalT mRNA in ovarian cancer cell lines was compared with the amount of GAT and total GalT in culture supernatant and (2) the concentration of GAT and total GalT in sera from the ovarian cancer patients was determined before and after the surgical resection. As the result, (1) the expression of GalT mRNA in cell lines was in agreement with the amount of GAT or total GalT released, and (2) the assay of GAT or total GalT in the sera showed that the tumor resection resulted in the rapid decrease of GAT,meantime the amount of total GalT did not reflect the tumor status, suggesting that GAT were released mainly from the tumor cells and in the serum the GalT from several tissues modified the concentration of the total GalT. Less
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