INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN (IGFBP) INHIBITS IGF ACTION ON HUMAN OSTEOSARCOMA CELLS

The influence of a human insulin-like growth factor binding protein, hIGFBP-1, on the action of IGFs on human osteosarcoma cells was examined. hIGFBP-1 was found to block binding of IGFs to their receptors on MG-63 cells and subsequent IGF stimulation of DNA synthesis. Concurrent incubation of hIGFBP-1 with either I-125-IGF-I or I-125-IGF-II prevented the binding of both I-125-IGFs to cells in a dose-dependent manner. hIGFBP-1 inhibition of IGF binding occurred similarly under both 4-degrees and 37-degrees-C conditions. Additionally, hIGFBP-1 facilitated the dissociation of IGFs bound to cells. The inhibitory effect of hIGFBP-1 on IGF-1 mediated H-3-thymidine incorporation into DNA was dose dependent. hIGFBP-1 did not inhibit binding to or stimulation of growth in MG-63 cells by des3-IGF-I, an IGF-I analog with a 100-fold less affinity for hIGFBP-I. This confirmed that hIGFBP-1 competed for IGF receptor binding sites on MG-63. Since hIGFBP-1 did not bind to cells, inhibition of IGF action was indirect, presumably through the formation of extracellular soluble bioinactive IGF-BP complexes.