Regulation of low-density lipoprotein metabolism by cell density and proliferative state

Stimulation of the proliferation of human skin fibroblasts by platelet-derived growth factor increased the binding and degradation of low-density lipoproteins at cell densities of 2000-30,000 cells/cm2. Binding and degradation of low-density lipoprotein was an inverse function of cell density in both proliferating and quiescent cells, indicating that the effect of cell density on the LDL receptor has proliferation-dependent and proliferation-independent components. The effect of medium conditioned by confluent fibroblasts on LDL metabolism was tested to determine if the effects of cell density on LDL metabolism might be mediated by cellular secretion products. Fibroblast-conditioned medium increased LDL metabolism, suggesting secretion products do not mediate these effects of cell density. These data indicate that regulation of the low-density lipoprotein receptor is not a simple on/off response to growth stimulation, but is responsive to extracellular cues such as cell density.