GANGLIOSIDE G(M3) INHIBITS THE PROLIFERATION OF CULTURED KERATINOCYTES

Ganglioside G(M3) is the predominant ganglioside of keratinocyte membr anes. It has been proposed in other cell types that G(M3) may particip ate in the regulation of cell proliferation. To examine the role of G( M3) in keratinocyte proliferation, purified G(M3) was added to culture d keratinocytes from normal foreskin, from lesional skin of patients w ith psoriasis and ichthyosis, and to cutaneous squamous carcinoma cell lines. Supplemental G(M3) inhibited the growth of all cultured kerati nocytes in a dose-dependent manner at concentrations of 10 - 100 muM. Keratinocytes from patients with psoriasis and ichthyosis were most se nsitive to the inhibitory effects of G(M3), and confluent undifferenti ated keratinocytes were least sensitive. No change in differentiation was noted after addition of G(M3). G(D3), 9-0-acetyl-G(D3), and G(D1b) also inhibited keratinocyte proliferation. Gangliosides G(M1) and G(D 1a) and sialic acid had little effect. Addition of 50 muM H-3-G(M3) to cultured keratinocytes resulted in 1.7 times the amount of cellular G (M3). These data suggest that hematoside (G(M3)) and ''b'' pathway gan gliosides (G(D3), G(D1b)), generated by the preferential activation of sialyltransferase II versus N-acetylgalactosaminyltransferase, may be involved in control of keratinocyte growth but not of differentiation .