Role of cell surface carbohydrates and proteins in cell behavior: studies on the biochemical reversion of an N-acetylglucosamine-deficient fibroblast mutant.

Abstract

AD6, a mutant derived from 3T3 Balb/c cells [mouse embryo fibroblast], is characterized by low adhesion to substratum, round shape, increase in surface microvilli, increase in agglutinability by concanavalin A and loss of directional motility. These properties are often observed in transformed cells. The mutant has normal growth properties and anchorage-dependence of growth, and it does not form tumors. In AD6, the biosynthesis of complex carbohydrates and glycoproteins is impaired because of a block in the acetylation of GlcN-6-P [glucosamine-6-phosphate]. This defect is responsible for all the surface alterations because feeding of GlcNAc [N-acetyl-glucosamine] to AD6 cells corrects the defects in the synthesis of complex carbohydrates and the exposure of glycoproteins at the outer surface of the plasma membrane. Parallel to this biochemical reversion, there is full restoration of the altered biological properties. In contrast, GlcNAc has no effect on the morphologic features of 2 lines of transformed cells. The carbohydrate portion of cell surface proteins may have an important role in adhesion and related aspects of cell behavior. The fact that a defined alteration of the cell surface induces many properties often encountered in transformed cells, without affecting control of cell division, strongly suggests that these alterations in properties are not sufficient to account for the loss of growth regulation.