Isoglobotetraosylceramide is a marker for highly metastatic cells in rat mammary adenocarcinomas.
We have previously identified a neutral glycolipid antigen which appears to be a surface antigenic marker for the metastatic subpopulation in the R3230AC rat mammary adenocarcinoma (S.A. Carlsen, M. Barry, and K. Newton, Clin. Exp. Metastasis, 8: 141-151, 1990). In this article we describe the structural characterization of this glycolipid antigen. The sequence of the sugars in the saccharide portion of the molecule was determined by specific glycosidase cleavage and further confirmed by mass spectroscopic analysis. The nature of the linkages between the monosaccharide units was determined by methylation analysis. The final structure was confirmed by NMR analysis and found to be isoglobotetraosylceramide (GalNAc beta 1-3Gal alpha 1-3Gal beta 1-4Gle beta 1-O-ceramide). We also present evidence that the cells marked by this antigen have a higher metastatic potential than the cells lacking this glycolipid as measured by the formation of lung colonies after i.v. injection of the cells into the tail vein of the rat. Furthermore, isoglobotetraosylceramide seems to play a direct role in the metastatic process since the blocking of exposed antigen with monoclonal antibodies, or their Fab fragments, results in a highly significant decrease in lung colony formation.
Carlsen
S A
SA
Department of Microbiology, University of Saskatchewan, Saskatoon, Canada.
Xie
Y
Y
Whitfield
D M
DM
Pang
H
H
Krepinsky
J J
JJ
D000230:Adenocarcinoma / Q000737:chemistry* / Q000556:secondary; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D005915:Globosides / Q000032:analysis*; D008175:Lung Neoplasms / Q000556:secondary; D009682:Magnetic Resonance Spectroscopy; D015674:Mammary Neoplasms, Animal / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D014410:Tumor Stem Cell Assay
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005915:Globosides; C004642:cytolipin R