AbstractThe 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 either125I‐IGF‐I or125I‐IGF‐II prevented the binding of both125I‐IGFs to cells in a dose‐dependent manner. hIGFBP‐1 inhibition of IGF binding occurred similarly under both 4° and 37°C conditions. Additionally, hIGFBP‐1 facilitated the dissociation of IGFs bound to cells. The inhibitory effect of hIGFBP‐1 on IGF‐1 mediated3H‐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
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