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Had-1, a uridine 5'-diphosphogalactose transport-defective mutant of mouse mammary tumor cell FM3A: composition of glycolipids, cell growth inhibition by lactosylceramide, and loss of tumorigenicity.

Abstract
Glycolipid compositions of mouse mammary tumor cell FM3A and its Newcastle disease virus-resistant mutant cell, Had-1, which was also characterized as a defective mutant of UDP-galactose transport to Golgi apparatus, have been studied. The major neutral glycolipid in FM3A was Gal beta 1-4Glc beta 1-1Cer (LacCer) (95%) and the rest was Glc beta 1-1Cer. The concentration of neutral glycolipids in Had-1 was only about one-fifth of that in FM3A. GlcB1-1Cer in Had-1 accounted for 79% of neutral glycolipids and the rest was LacCer, the content of which was decreased to 4% of that in FM3A. Ganglioside patterns of the two cell lines were similar, although gangliosides with N-glycolylneuraminic acid were increased in Had-1 cells compared with that in FM3A cells. The presence of NeuAc alpha 2-3-Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer, NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-2Cer, GM3, and GD3 was demonstrated by thin-layer chromatography immunostaining. 125I-Labeled Newcastle disease virus bound only poorly to gangliosides extracted from either FM3A or Had-1 cells on a high performance thin-layer chromatography plate. The effects of glycolipids on the growth of the two cell lines were also studied. Had-1 cells were more sensitive to glycolipids added exogenously than FM3A cells. Addition of GM3 had a stimulative effect on cell growth of Had-1. LacCer, Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 4-1Cer, and Glc beta 1-1Cer inhibited the growth of Had-1 cells. LacCer was the most potent inhibitor. LacCer immobilized on the culture plate also inhibited the growth of Had-1 cells. The inhibitory effect was recovered completely overcome by transferring the cells to LacCer-free medium. Had-1 cells were not tumorigenic in C3H/He mice, and furthermore the tumorigenic activity of FM3A cells was suppressed by the prior administration of Had-1 cells.
AuthorsT Taki, K Ogura, C Rokukawa, T Hara, M Kawakita, T Endo, A Kobata, S Handa
JournalCancer research (Cancer Res) Vol. 51 Issue 6 Pg. 1701-7 (Mar 15 1991) ISSN: 0008-5472 [Print] United States
PMID1998961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD
  • Glycolipids
  • Glycosphingolipids
  • Lactosylceramides
  • Uridine Diphosphate Galactose
  • CDw17 antigen
Topics
  • Animals
  • Antigens, CD
  • Cell Aggregation (drug effects)
  • Cell Division (drug effects)
  • Chromatography, Thin Layer
  • Female
  • Glycolipids (analysis)
  • Glycosphingolipids (pharmacology)
  • Killer Cells, Natural (immunology)
  • Lactosylceramides
  • Mammary Neoplasms, Experimental (chemistry, pathology)
  • Mice
  • Mice, Inbred C3H
  • Mutation
  • Neoplasm Transplantation
  • Newcastle disease virus (metabolism)
  • Tumor Cells, Cultured
  • Uridine Diphosphate Galactose (metabolism)

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