Sequential addition of platelet factor and plasma to BALB/c 3T3 fibroblast cultures stimulates somatomedin-C binding early in cell cycle

Abstract

Recent studies have shown that confluent cultured fibroblasts must be rendered competent by a factor contained in platelets before they can respond to plasma components and progress from G0 to S phase of the cell cycle. Somatomedin-C is one of the components of platelet-poor plasma necessary for cell cycle progression, but other factors present in somatomedin-C-deficient plasma are also required. Because both competence and progression factors contained in somatomedin-C-deficient serum modulate somatomedin-C action in fibroblasts, this study was undertaken to examine their possible influence on the binding of 125I-labeled somatomedin-C. Exposure of BALB/c 3T3 fibroblasts to high concentrations of platelet-derived growth factor alone prevented the time-dependent decrease in somatomedin-C binding which occurs in serum-free medium. Lower concentrations of the growth factor or 5% (vol/vol) platelet-poor plasma reduced but did not abolish this decrease. In contrast, sequential addition of platelet-derived growth factor followed by platelet-poor plasma resulted in a 75% increase in 125I-labeled somatomedin-C binding over basal levels during the first 2 hr. Binding increased by 125% when somatomedin-C-deficient platelet-poor plasma was substituted for normal platelet-poor plasma. The hormonal induction of somatomedin-C receptors appears to be a mechanism whereby peptide growth factors such as platelet-derived growth factor may condition the cell to respond optimally to somatomedin-C.