Characteristic expression of Lewis-antigenic glycolipids in human ovarian carcinoma-derived cells with anticancer drug-resistance.
By comparing ovarian carcinoma-derived KF28 cells with the corresponding anticancer drug-resistant cells, the taxol- and cisplatin-resistant properties were found to be closely related with MDR1 and BSEP, and MRP2 transporters, respectively. In addition to the transporters expression, the amounts of glycolipids, particularly their longer carbohydrate structures, in the resistant cells increased to 3-4-fold of those in the sensitive cells due to enhanced transcription of the respective glycosyltransferases. The major glycolipids in the sensitive and resistant cells were GlcCer and Gb(3)Cer, respectively, and extension of the carbohydrate structure into Lewis antigen characteristically occurred in the resistant cells. Le(b), which was not detected in the cisplatin-resistant cells, was present in the taxol-resistant cells, while Le(x) was present in the cisplatin-resistant cells at a higher concentration than in the taxol-resistant cells. 2-Hydroxy fatty acids were significantly abundant in glycolipids of the resistant cells, but they were not detected in free ceramides or sphingomyelin, indicating that the enhanced synthesis of glycolipids in the resistant cells was not linked with the removal pathway for virulent ceramides derived from sphingomyelin. The resistant cells with abundant glycolipids exhibited lower membrane fluidity than the KF28 cells, and this property might be involved in the anticancer drug-resistance.
Iwamori
Masao
M
Department of Biochemistry, Faculty of Science and Technology, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502, Japan. iwamori@life.kindai.ac.jp
Iwamori
Yuriko
Y
Kubushiro
Kaneyuki
K
Ishiwata
Isamu
I
Kiguchi
Kazushige
K
D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005963:Glucosylceramides / Q000096:biosynthesis; D006017:Glycolipids / Q000096:biosynthesis*; D016695:Glycosyltransferases / Q000235:genetics; D006801:Humans; D007790:Lactosylceramides / Q000096:biosynthesis; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis*; D016256:Lewis X Antigen / Q000096:biosynthesis; D009844:Oligosaccharides / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D013107:Sphingolipids / Q000737:chemistry; D014281:Trihexosylceramides / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
C500822:3-aminopropyl fucopyranosyl-1-2-galactopyranosyl-1-3-(fucopyranosyl-1-4)-2-acetamido-2-deoxyglucopyranosyl-1-3-galactopyranosyl-1-4-glucopyranoside; D005227:Fatty Acids; D005963:Glucosylceramides; D006017:Glycolipids; D007790:Lactosylceramides; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D009844:Oligosaccharides; D013107:Sphingolipids; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D016695:Glycosyltransferases; D017239:Paclitaxel; D002945:Cisplatin