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 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.
Campbell
P G
PG
Orthopaedic Research Laboratory, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania 15212.
Novak
J F
JF
D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017451:Receptors, Somatomedin; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA