DIFFERENCE IN BIOLOGICAL EFFECTS BETWEEN INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 AND PROTEIN-3

Insulin-like growth factor binding proteins 1 and 3 are essentially known as regulators of IGF bioactivity. However, we previously showed that IGFBP-3 was able, in chick embryo fibroblast (CEF), to 100% inhibit DNA synthesis stimulated by calf serum, while the maximal inhibition found with IGFBP-1 was 60%, suggesting a difference between the two IGFBPs in their biological functions. Results of the present work agree with this assumption: (a) Recombinant human IGFBP-3, like rat IGFBP-3, was able to 100% inhibit DNA synthesis stimulation induced by human serum, while this stimulation was 75% decreased by IGFBP-1. However, the most striking difference was observed when the effects of the two IGFBPs were compared for stimulation induced by a serum growth factor (SGF) fraction depleted in IGFs. Stimulation induced by the SFG fraction was more significantly decreased (p < 0.001) by IGFBP-3 than by IGFBP-1. The mean percent inhibition +/- SEM was 67.1 +/- 2.5 in the presence of IGFBP-3 (200 ng/ml) and 29.3 +/- 2.7 and 34.2 +/- 4 in the presence of 200 and 400 ng/ml IGFBP-1 respectively. Inhibition by 200 ng/ml IGFBP-1 and inhibition by 6 ng/ml IGFBP-3 were additive. However, inhibition by IGFBP-3 and that by IGFBP-1 were no longer additive at high concentrations of IGFBP-3, which might thus replace IGFBP-1. (b) FGF stimulation of CEF was similarly inhibited (65% and 70%) by IGFBP-1 and IGFBP-3. (c) TGF beta stimulation of CEF was more strongly decreased by IGFBP-3 (90%) than by IGFB-1 (60%). (d) PDGF stimulation was poorly decreased by IGFBP-1 and IGFBP-3. The difference in biological effects that we observed between IGFBP-3 and IGFBP-1, particularly in terms of DNA synthesis stimulation induced by the SGF fraction, led us to assume that IGFBP-3 has multifunctional properties and has a function different from its known function to bind IGFs.