Insulin-like growth factor binding protein (IGFBP) inhibits IGF action on human osteosarcoma cells

• Published in: Journal of cellular physiology Vol. 149; no. 2; p. 293
• Main Authors: Campbell, P G, Novak, J F
• Format: Journal Article
• Language: English
• Published: United States 01-11-1991
• Subjects: Carrier Proteins - metabolism; Carrier Proteins - pharmacology; DNA - biosynthesis; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I - antagonists & inhibitors; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor II - antagonists & inhibitors; Insulin-Like Growth Factor II - metabolism; Osteosarcoma - metabolism; Receptors, Cell Surface - metabolism; Receptors, Somatomedin; Tumor Cells, Cultured
• DOI: 10.1002/jcp.1041490216
• ISSN: 0021-9541

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 125I-IGF-I or 125I-IGF-II prevented the binding of both 125I-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 3H-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-1, 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.