Glycosphingolipids of lectin-resistant mutants of the highly metastatic mouse tumor cell line, MDAY-D2.
Neutral and acidic glycolipids in MDAY-D2, a highly metastatic murine tumor cell line, were examined and compared with glycolipids of MDW4 and D33W25-1, two lectin-resistant mutants of MDAY-D2 from distinct genetic complementation classes. D33W25-1 remained highly metastatic while MDW4 cells were found to be nonmetastatic (Dennis, J. W., Donaghue, T., Florian, M., and Kerbel, R. S., Nature (Lond.), 292: 242-245, 1981 and Dennis, J. W. et al., Cancer Res., 46: 4594-4600, 1986). Glycolipid structures were identified by fast-atom bombardment mass spectrometry, methylation analysis, exoglycosidase treatment, and immunostaining. The metastatic MDAY-D2 was found to contain GM3, GM2, IV3GalNAc-GM1b, and high levels of GM1a, GM1b, and GD1a. MDW4 showed a 3-fold decrease in total ganglioside content compared to MDAY-D2 and a corresponding increase in the precursor, glucosylceramide. MDW4 was deficient in GM1 and accumulated GM2 and NeuNG-GM2, indicating a lack of gangliosides having NeuNAc alpha 2-3Gal beta 1-3 terminal sequence. Neosynthesis of GD3 was also observed in MDW4. The metastatic mutant D33W25-1 had a similar pattern of gangliosides as that found in MDAY-D2 cells with N-glycolyl rather than N-acetyl neuraminic acid. These results suggest that the metastatic property of these cell lines may be related to the level of ganglioside, and that the substitution of N-glycolyl for N-acetyl neuraminic acid does not reduce metastatic capacity.
D000818:Animals; D002460:Cell Line; D002855:Chromatography, Thin Layer; D005732:Gangliosides / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006028:Glycosphingolipids / Q000032:analysis*; D037102:Lectins / Q000494:pharmacology*; D013058:Mass Spectrometry; D051379:Mice; D008811:Mice, Inbred DBA; D009154:Mutation; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000032:analysis*
D005732:Gangliosides; D006023:Glycoproteins; D006028:Glycosphingolipids; D037102:Lectins