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Journal of Biochemistry Advance Access originally published online on December 26, 2006
Journal of Biochemistry 2007 141(3):309-317; doi:10.1093/jb/mvm031
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© 2006 The Japanese Biochemical Society.

Characteristic Expression of Lewis-antigenic Glycolipids in Human Ovarian Carcinoma-derived Cells with Anticancer Drug-resistance

Masao Iwamori1,*, Yuriko Iwamori1, Kaneyuki Kubushiro2, Isamu Ishiwata3 and Kazushige Kiguchi4

1Department of Biochemistry, Faculty of Science and Technology, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka 577-8502; 2Department of Obstetrics and Gynecology, Kawasaki Municipal Hospital, 12-1 Shinkawa-dori, Kawasaki-ku, Kawasaki, Kanagawa 210-0013; 3Ishiwata Gynecologic Hospital, 1-4-21 Kamimito, Mito, Ibaraki 310-0044; and 4Department of Obstetrics and Gynecology, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan

*To whom correspondence should be addressed. Tel: +81-6-6721-2332, Fax: +81-6-6723-6721, E-mail: iwamori{at}life.kindai.ac.jp

Received November 20, 2006; Accepted December 20, 2006


  Abstract

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 Gb3Cer, respectively, and extension of the carbohydrate structure into Lewis antigen characteristically occurred in the resistant cells. Leb, which was not detected in the cisplatin-resistant cells, was present in the taxol-resistant cells, while Lex 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.

Key Words: ceramides, glycolipids, glycosyltransferase genes, membrane fluidity, transporter proteins

Abbreviations: , The glycolipid nomenclature is based on the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature (1); FABMS, fast atom bombardment mass spectrometry; GC–MC, gas liquid chromatography–mass spectrometry; MDR, multidrug resistance; MPR, multidrug resistance-associated protein; BSEP, bile salt export pump; CMH, ceramide monohexoside; Le, Lewis antigen; CDH, ceramide dihexoside; CTH, ceramide trihexoside; RT-PCR, reverse transcriptase-polymerase chain reaction; BSA, bovine serum albumin


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