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

Highly sialylated gangliosides have been shown to alter cellular adhes ion to a fibronectin matrix. The effect of these gangliosides on the a dhesion, spreading, and migration of cultured keratinocytes on a fibro nectin 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 keratinocyte s to wells coated with laminin, type I or type IV collagen, 804G extra cellular matrix, or albumin, G(T1b) also inhibited keratinocyte migrat ion on fibronectin in a concentration-dependent manner at concentratio ns as low as 5 nM G(T1b), but had no effect on migration of keratinocy tes plated on other matrices, G(T1b) binds to intact fibronectin and t o the 120-kD RGDS-containing cell-binding fibronectin fragment, but no t to the heparinor gelatin-binding fragments of fibronectin. Although RGDS competes with G(T1b) in inhibiting adhesion, G(T1b) does not dimi nish binding of keratinocytes to a derivatized RGDS substratum, sugges ting that the G(T1b) effect involves a non-RGDS site in the cell-bindi ng region that modulates RGDS/a(5) beta(1) integrin receptor interacti on. Through a specific effect on keratinocyte interaction with fibrone ctin, G(T1b) map participate in the regulation of cell adhesion and mi gration on a fibronectin substratum, which are important events during wound healing and the spreading of cutaneous neoplasia.