Persistence of the mitogenic response to platelet-derived growth factor (competence) does not reflect a long-term interaction between the growth factor and the target cell

Abstract

Quiescent BALB/c-3T3 cells exposed briefly to platelet-derived growth factor (PDGF) become 'competent' to replicate their DNA even if PDGF is removed from cell culture medium prior to the onset of DNA synthesis. We have suggested that persistence of the PDGF-induced competent state reflects a rapidly induced and relatively stable biochemical change within the target cells. Others suggest that the phenomenon reflects a long-term association between PDGF and its target cells or perhaps between PDGF and the cell culture dish. This controversy has been addressed by examining the effect of anti-PDGF antibodies on PDGF-induced competence and by studying the chemical fate of 125I-labeled PDGF. Anti-PDGF antibodies inactivate both soluble and surface-bound PDGF. However, if quiescent 3T3 cells are exposed to PDGF for as little as 30 min, subsequent addition of these antibodies to the culture medium does not prevent the mitogenic response. Under conditions where the PDGF-induced competent state decays stochastically with a t(1/2) of 18-20 h, cell-associated 125I-PDGF decays with a t(1/2) of ~50 min. These data do not support the concept that persistence of the PDGF-induced competent state reflects a long-term association between PDGF and the target cells or between PDGF and the culture dish.