STIMULATION BY TGF-BETA OF CHICK-EMBRYO FIBROBLASTS-INHIBITION BY AN IGFBP-3

The multiple effects of TGFβ on cell proliferation are not well understood. Our results show that TGFβ was a good but transient mitogen for chick embryo flbroblasts. DNA synthesis was three- to fourfold increased, even at high concentrations of TGFβ. We did not show a bimodal effect. An inhibitor of cell growth, that inhibits 100% of stimulation induced by serum in CEF, was purified to homogeneity from medium conditioned by mouse 3T3 cells. This inhibitor has been shown to be an IGF-binding protein (mIGFBP-3). In the present work, this mIGFBP-3 inhibited the TGFβ stimulation by about 50%, while the stimulation induced by PDGF or insulin was not inhibited by mIGFBP-3. Furthermore, TGFβ stimulation, in the presence of a high concentration of insulin in conditions which would saturate IGF receptors, was not significantly inhibited by mIGFBP-3. All together these results suggest that a part of the mitogenic effect of TGFβ may be through increasing IGF secretion and eventually other growth factors such as PDGF (as suggested previously). © 1992.