Roles of Gangliosides in the Surface Properties of Normal and Malignant Cells

Abstract

Gangliosides are ubiquitous plasma membrane components whose structural characteristics make it possible to establish multiple interactions with the pericellular microenvironment. Several receptorial activities of gangliosides have already been recognized and the possible involvement of gangliosides in growth control, adhesion, differentiation, and immunologic recognition is at present under study. The study of the role of gangliosides in cell growth control has been approached in our laboratory by investigating whether the ganglioside changes found in SV40-transformed Balb/c3T3 cells (SV3T3 cells) revert to a normal pattern in a variant of SV3T3 cells with growth properties similar to those of normal parental cells, the concanavalin A-selected SV3T3 revertant cells. These latter cells showed the same reduction of the more complex gangliosides as found in SV3T3 cells, while their amount of II3NeuAC-LacCer (GM3) was greatly increased compared to that found in either normal or transformed 3T3 cells. In order to study the role of gangliosides in the adhesion process, we analyzed the ganglioside structure of the so-called substrate-attached material, a cell surface structure involved in the adhesion of cells to substrate, from cultures of Balb/c3T3, SV3T3, and concanavalin A-selected SV3T3 revertant cells and from cultures of a system of transformed cells with different metastatic potential: the nonmetastatic B77-3T3 and the highly metastatic AA6 cells. Compared to normal cells, all the transformed cells contained smaller quantities of gangliosides in their substrate-attached material. In both normal and transformed cell lines, the gangliosides of the substrate-attached material, compared to those of detached cells, were found to be enriched by IV3NeuAC, II3NeuAc-GgOse4Cer (GD1a); the only exception were the AA6 cells which contained rather low levels of GD1a in both detached cells and substrate-attached material. When ganglioside compositions of the substrate-attached material, detached cells, and plasma membranes were compared in Balb/c3T3, SV3T3, and concanavalin A-selected SV3T3 revertant cells, a prevalence of GD1a was noted in the substrate-attached material and not in the plasma membranes. Moreover, the level of GD1a was scarcely modified in the substrate-attached material from cultures of a neuroblastoma cell line after growth in media containing chelating agents, a treatment which is known to modify the composition of cellular gangliosides. The overall indications emerging from these findings suggest a role for GM3 in growth control and a role for complex gangliosides in the adhesion process.