Specific interaction between gangliotriaosylceramide (Gg3) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells.
In view of the possible role of glycosphingolipids in defining the specificity of cell-cell interactions, the key molecules for recognition of cell surface glycosphingolipids have been studied. In addition to previously suggested recognition mechanisms involving endogenous lectins and glycosyltransferases, an alternative possibility, based on carbohydrate-carbohydrate (Lex-Lex) interaction, has been raised (Eggens, I., Fenderson, B., Toyokuni, T., Dean, B., Stroud, M., and Hakomori, S. (1989) J. Biol. Chem. 264, 9476-9484). We now report a highly specific interaction between gangliotriaosylceramide (Gg3, GalNAc beta 1----4Gal beta 1----4Glc beta 1----Cer) and sialosyllactosylceramide (GM3, NeuAc alpha 2----3Gal beta 1----4Glc beta 1----Cer). The interaction requires a bivalent cation (Ca2+ or Mg2+) and can be inhibited by sialosyl 2----3 lactose, anti-GM3 antibody (DH2), anti-Gg3 antibody (2D4), or EDTA. The strength of interaction between GM3 liposome and the Gg3-coated plastic surface was highly density-dependent. The mouse lymphoma L5178 AA12 cell line (high expressor of Gg3) interacted specifically with the mouse B16 melanoma cell line (high expressor of GM3). The interaction was inhibited by 5 mM sialosyllactose, anti-GM3 antibody, anti-Gg3 antibody, and EDTA in analogy to GM3-Gg3 interaction. L5178 AV27, a genetically related variant clone which does not express Gg3, showed no interaction with B16 cells. Untreated AA12 cells, but not 2D4-treated AA12 cells or AV27 cells, interacted with GM3 coated on the plastic surface. These findings suggest a specific interaction between AA12 cells and B16 cells based on Gg3-GM3 interaction.
Kojima
N
N
Biomembrane Institute, Seattle, Washington.
Hakomori
S
S
D000818:Animals; D002240:Carbohydrate Sequence; D002450:Cell Communication; D005679:G(M3) Ganglioside / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism*; D007700:Kinetics; D007940:Leukemia L5178 / Q000503:physiopathology*; D007942:Leukemia, Experimental / Q000503:physiopathology*; D008081:Liposomes; D008546:Melanoma, Experimental / Q000503:physiopathology*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D014407:Tumor Cells, Cultured / Q000502:physiology
D005679:G(M3) Ganglioside; D005732:Gangliosides; D008081:Liposomes