Growth factor-induced proliferation of human fibroblasts in serum-free culture depends on cell density and extracellular calcium concentration.
Human neonatal skin fibroblasts plated sparsely in MCDB 105 traversed a complete cell cycle in the absence of serum or serum-derived proteins. Addition of pure PDGF did not significantly increase entrance into S phase as revealed by 3H-thymidine labeling index or clonal growth on palladium islands. In subphysiologic Ca2+ concentrations or in the presence of a calmodulin inhibitor, W7, proliferation in the absence of growth factors ceased and PDGF became mitogenic. In contrast, confluent fibroblast cultures were stimulated by PDGF in physiologic Ca2+ concentrations. This was also the case with sparse adult skin fibroblast cultures while a fetal strain entered S in the absence of PDGF even in low extracellular Ca2+ concentrations. EGF gave similar results as PDGF in all experiments performed. This proposes a similar role for the two growth factors in the cell cycle. However, a difference in the mechanisms of action of PDGF and EGF is indicated by the fact that PDGF and EGF were additive at optimal concentrations when maximal growth response by a single growth factor was restricted by a subphysiologic extracellular Ca2+ concentration.
D000367:Age Factors; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000097:blood; D006801:Humans; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D013449:Sulfonamides; D004815:Epidermal Growth Factor; C017967:W 7; D004247:DNA; D002118:Calcium