Stimulation of Division of Density Inhibited Fibroblasts Glucocorticoids

Abstract

THE division of most “normal” cells in culture is inhibited after they have grown to a confluent monolayer. This is not the case with cells transformed either spontaneously or by tumour viruses¹. Alterations of the surface membrane might be partly responsible for this uncontrolled growth²: for example, protease action at the surface of contact-inhibited cells causes them to divide^3,4 and acquire surface properties characteristic of malignant cells, such as increased agglutinability by plant lectins^5,6. Neuraminidase⁷ and hyaluronidase⁸ can also initiate division of contact-inhibited cells. Transformed cells contain abnormally large concentrations of proteases and glycosidases^9,10 which are presumed to be lysosomal enzymes. Since cortisol stabilizes lysosomal membranes¹¹, we decided to investigate its effect on the growth of cells not subject to density inhibition of division: we found very little effect on 3T6, L, polyoma-transformed 3T3 (Py3T3) and SV40-trans-formed 3T3 (SV3T3) cells. However, cortisol unexpectedly stimulated DNA synthesis and division of density-inhibited 3T3 cells. This stimulation was specific for cells subject to contact inhibition of division. Density-inhibited early passage diploid human foreskin fibroblasts (HF cells) were similarly stimulated by cortisol. In addition, the stimulation was specific for steroids with high levels of glucocorticoid activity. The stimulation appears to involve changes in the cell surface, for treated 3T3 cells were agglutinated to a greater degree by concanavalin A than control cells.