GANGLIOSIDE GT(1B) INHIBITS KERATINOCYTE ADHESION AND MIGRATION ON A FIBRONECTIN MATRIX

Highly sialylated gangliosides have been shown to alter cellular adhesion to a fibronectin matrix. The effect of these gangliosides on the adhesion, spreading, and migration of cultured keratinocytes on a fibronectin matrix has not been explored. Ganglioside G(T1b) significantly prevented attachment of keratinocytes to fibronectin and also detached previously adherent keratinocytes in a concentration-dependent manner without cell toxicity. G(T1b) did not affect adhesion of keratinocytes to wells coated with laminin, type I or type IV collagen, 804G extracellular matrix, or albumin, G(T1b) also inhibited keratinocyte migration on fibronectin in a concentration-dependent manner at concentrations as low as 5 nM G(T1b), but had no effect on migration of keratinocytes plated on other matrices, G(T1b) binds to intact fibronectin and to the 120-kD RGDS-containing cell-binding fibronectin fragment, but not to the heparinor gelatin-binding fragments of fibronectin. Although RGDS competes with G(T1b) in inhibiting adhesion, G(T1b) does not diminish binding of keratinocytes to a derivatized RGDS substratum, suggesting that the G(T1b) effect involves a non-RGDS site in the cell-binding region that modulates RGDS/a(5) beta(1) integrin receptor interaction. Through a specific effect on keratinocyte interaction with fibronectin, G(T1b) map participate in the regulation of cell adhesion and migration on a fibronectin substratum, which are important events during wound healing and the spreading of cutaneous neoplasia.