Insulinlike growth factor I: a potent mitogen for human osteogenic sarcoma.
Insulinlike growth factor I (IGF-I) is among the peptide mitogens that play key roles in the regulation of normal skeletal growth. To investigate the possibility that certain skeletal neoplasms retain a sensitivity to mitogenic stimulation by IGF-I, we studied the effects of this growth factor on human osteosarcoma. Competitive-binding assays and affinity-labeling experiments on membranes prepared from MG-63 immortalized human osteosarcoma cells and primary human osteogenic sarcoma cells demonstrate the presence of specific IGF-I receptors. Furthermore, we show that IGF-I is a potent stimulator of proliferation of MG-63 cells in vitro and is active at concentrations as low as 10(-10) M. A blocking antibody against the IGF-I receptor (alpha-IR3) significantly reduces IGF-I-stimulated proliferation in a dose-dependent manner. These results are consistent with the hypothesis that at least a subset of human osteogenic sarcomas are responsive to IGF-I and indicate that it may be possible to exploit this responsiveness therapeutically.
Pollak
M N
MN
Department of Medicine, McGill University, Montreal, Canada.
Polychronakos
C
C
Richard
M
M
D000345:Affinity Labels; D001667:Binding, Competitive; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000345:Affinity Labels; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I