Comparison of the type-2 insulin-like growth factor receptor in normal osteoblasts and osteosarcoma-derived osteoblast-like cells.
Insulin-like growth factor-II is known to stimulate the proliferation and differentiation of osteoblasts in part through activation of the type-2 insulin-like growth factor receptor. The present study examined the type-2 insulin-like growth factor receptors of three normal osteoblast-like cells and three osteosarcoma-derived osteoblast-like cells (OGA, SU, and IMAI) from humans. [125I]insulin-like growth factor-II was used for the binding studies. All of the cell types had high affinity binding sites for insulin-like growth factor-II (dissociation constants [Kd] < or = 1 nM). The concentration of these sites was 10 to 24-fold higher in normal osteoblasts than in the osteosarcoma cells studied. Unlabeled insulin-like growth factor-II inhibited the binding of [125I]insulin-like growth factor-II to the cells in a dose-dependent manner; however, unlabeled insulin-like growth factor-I and insulin were less effective. Covalent crosslinking of insulin-like growth factor-II binding sites gave molecular mass estimates of M(r) 250,000 in human osteoblast cells, 250,000 and 130,000 in OGA cells, 240,000 in SU cells, and 250,000 and 130,000 in IMAI cells. Unlabeled insulin-like growth factor-II inhibited all affinity labeling. In Northern blot analysis, the type-2 insulin-like growth factor receptor mRNA of normal osteoblasts was seen in greater abundance than it was in osteosarcoma cells. These results indicate that the numbers of type-2 insulin-like growth factor receptors differ between normal and transformed osteoblasts and that the differential expression of the receptor may be due to the differentiation of osteoblasts.
D000293:Adolescent; D000328:Adult; D000345:Affinity Labels; D001667:Binding, Competitive; D015152:Blotting, Northern; D001859:Bone Neoplasms / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D000345:Affinity Labels; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II