Alterations in the glycolipid composition and cellular properties of ovarian carcinoma-derived RMG-1 cells on transfection of the alpha1,2-fucosyltransferase gene.
Transfection of the mouse Fut1 and Fut2, and human FUT1 genes into human ovarian carcinoma-derived RMG-1 cells resulted in 20-30-fold increases in cellular alpha1,2-fucosyltransferase activity, and in alteration of the glycolipid composition, including not only fucosylated products, but also precursor glycolipids. Although globo-series glycolipids were not significantly affected by the transfection, the major glycolipids belonging to the lacto-series type 1 chain family in RMG-1 cells and the transfectants were the Lc4Cer, Lewis a (Le)a and Leb, and H-1 glycolipids, respectively, suggesting that fucosylation of Lc4Cer to the H-1 glycolipid prevents the further modification of Lc4Cer to Lea and Leb in the transfectants. Also, the lacto-series type 2 chains in RMG-1 cells were LeX, NeuAc-nLc4Cer and NeuAc-LeX, and those in the transfectants were LeX and LeY, indicating that the sialylation of nLc4Cer and LeX is restricted by increased fucosylation of LeX. As a result, the amount of sialic acid released by sialidase from the transfectants decreased to 70% of that from RMG-1 cells, and several membrane-mediated phenomena, such as the cell-to-cell interaction between cancer cells and mesothelial cells, and the cell viability in the presence of an anticancer drug, 5-fluorouracil, for the transfectants was found to be increased in comparison to that for RMG-1 cells. These findings indicate that cell surface carbohydrates are involved in the biological properties, including cell-to-cell adhesion and drug resistance, of cancer cells.
Iwamori
Masao
M
Department of Biochemistry, Faculty of Science and Technology, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502.
Tanaka
Kyoko
K
Kubushiro
Kaneyuki
K
Lin
Bei
B
Kiguchi
Kazushige
K
Ishiwata
Isamu
I
Tsukazaki
Katsumi
K
Nozawa
Shiro
S
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D005260:Female; D005647:Fucosyltransferases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000503:physiopathology*; D014162:Transfection; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D005647:Fucosyltransferases; D006017:Glycolipids; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase; D000097631:Galactoside 2-alpha-L-fucosyltransferase