Filopodia number increases with age and quiescence in populations of normal WI-38 cells, and is correlated with drug-induced changes in proliferation in both normal and transformed populations

Abstract

Filopodia in log and stationary phase populations of human fetal lung fibroblasts (WI-38) at low and high population doubling levels (PDLs), and of SV40 transformed WI-38 cells (VA13A), were observed and counted under different conditions of in vitro growth by scanning electron microscopy. Cells from old non-vigorously growing WI-38 populations (those at a high PDL) had more filopodia than younger populations (those at a lower PDL) at all times after seeding, and for any given population stationary phase cells (those entering, or in, quiescence), had more than log phase cells. Hydrocortisone (HC, 14 μM), which stimulates proliferation and increases life span of WI-38 cells, was associated with a marked decrease in filopodia. Conversely, retinoic acid (RA, 10 μM), which inhibits growth and decreases life span of WI-38 cells, was associated with an increase in filopodia. Since old cell populations have lower saturation densities than young, it is suggested that cell contact signaling growth cessation in these populations may be mediated by filopodia. The HC-associated decrease in filopodia may thus be possibly interpreted as a decrease in filopodia-mediated “density dependent inhibition,” and the increase in filopodia with RA as a possible increase in this “inhibition.” Both HC and RA inhibit growth and are associated with an increase in filopodia in VA13A cultures.