CDGF (chicken embryo fibroblast-derived growth factor) is mitogenically related to TGF-beta and modulates PDGF, bFGF,...

Chicken embryo fibroblast (CEF)-derived growth factor (CDGF), which was recently isolated from serum-free conditioned medium (SFCM) of confluent primary cultures of CEF (A. Geistlich and H. Gehring, Eur. J. Biochem. 207, 147-153, 1992), exhibited a strong mitogenic activity on sparse cultures of NIH/3T3 cells. The activity of CDGF was different from that of SFCM; i.e., the onset of DNA synthesis was delayed for about 7 h. CDGF induced maximally 25% of the activity of serum or SFCM if the activity was measured with a 2-h[3H]thymidine pulse starting 15 h after stimulation of the cells, indicating loss of a protein which modulated the mitogenic activity of CDGF. However, [3H]-thymidine incorporation of cells stimulated with approximately 50 pM CDGF reached serum values after prolongation of the thymidine pulse to 24 h. PDGF, at a concentration of approximately 300 pM, and bFGF (approximately 10 pM) exhibited strong activities in the 2-h pulse, whereas TGF-beta behaved like CDGF. IGF-I induced [3H]thymidine incorporation only weakly and only in the 2-h pulse. EGF did not induce any [3H]thymidine incorporation at all. CDGF together with small concentrations of bFGF (3.5 pM), higher concentrations of PDGF (300 pM), or IGF-I (1 nM) increased synergistically thymidine incorporation in the 2-h pulse, exceeding in the case of PDGF and bFGF the values obtained with 10% serum. Such a synergism could not be demonstrated with alpha-fetoprotein or fetuin, two serum proteins which have been reported to cooperate with growth factors. Regarding induction of cellular growth, only PDGF proved similar to serum, whereas cells stimulated with CDGF or TGF-beta showed a decreased rate of multiplication during the first day after stimulation. After this lag, however, CDGF- and TGF-beta-stimulated cells grew also with a rate similar to that obtained with serum, indicating the induction of an autocrine mitogen by CDGF or TGF-beta. FGF, IGF-I, and PDGF all enhanced CDGF-induced cell growth during the first day, whereas an additive stimulation over at least 2 days was observed with PDGF. CDGF behaved similar to TGF-beta in the synergism with IGF-I.