Biologic roles of gangliosides GM(3) and G(D3) in the attachment of human melanoma cells to extracellular matrix proteins

The biologic functions of gangliosides G(M3) and G(D3) in the attachment of human melanoma cells to extracellular matrix proteins (type I and TV colla gens, fibronectin, and laminin) were investigated by using the G(D3)-defici ent mutant clone (SK-MEL-28-N1) and the parent cell line SK-MEL28, SK-MEL-2 8-N1 (N1) (high G(M3) expression: G(M3), 97.3%; G(D3), 0%) Was selected by treating SK-MEG 28 (high G(D3) but low G(M3): G(M3), 6.5%, G(D3), 93.5%) wi th an anti-G(D3) monoclonal antibody (R24) and rabbit complement and subseq uent subcloning of the surviving cells. The N1 clone showed significantly h igher ability to adhere to type I and IV collagens and laminin than the par ent clone SK-MEL-28, In the N1 clone, the expression of alpha 2 beta 1 and alpha 3 beta 1 integrin receptors was increased, whereas in SK-MEL28, their expression was very low or undetectable. The treatment with monoclonal ant ibodies directed specifically to G(D3) expressed on SK-MEL28 inhibited the cell attachment to type TV collagen (33% inhibition of control), fibronecti n (59%), and laminin (71%). These findings suggest that gangliosides G(M3) (by influencing integrin receptor levels) and G(D3) (by interacting directl y with matrix proteins) might play some functional roles in attachment to e xtracellular matrix proteins and thereby enhance the metastatic potency of melanoma cells.