Specific receptors for epidermal growth factor in human bone tumour cells and its effect on synthesis of prostaglandin E2 by cultured osteosarcoma cell line.
Using tumour cell lines derived from human bone tumours, specific binding sites for epidermal growth factor (EGF), a potent growth stimulator in many tissues, and its effect on synthesis of prostaglandin (PG) E2, a potent bone-resorbing factor, by cultured osteosarcoma cell line were studied. Three tumour cell lines, one osteosarcoma (HOSO) and two giant cell tumours of the bone (G-1 and G-2), all possessed specific binding sites for 125I-labelled EGF: the apparent dissociation constant was approximately 4-10 X 10(-10) M and the maximal binding capacity was 50 000-80 000 sites/cell. EGF had no mitogenic effect in these cell lines. However, these cell lines did not have specific binding sites for 125I-labelled parathyroid hormone (PTH) or calcitonin. HOSO line produced and secreted PGE2 into medium, while no significant amount of PGE2 was demonstrated in G-1 or G-2 line. EGF significantly stimulated PGE2 production in HOSO line in a dose-dependent manner (0.5-50 ng/ml); its stimulatory effect was completely abolished by indomethacin, an inhibitor of PG biosynthesis. Exogenous PGE1 significantly stimulated cyclic AMP formation in HOSO line, whereas PGF2 alpha, PTH, calcitonin, or EGF had no effect. None of these calcium-regulating hormones affected cyclic AMP generation in either G-1 or G-2 line. These data indicate that human bone tumour cells have specific EGF receptors unrelated to cell growth, and suggest that EGF may be involved in bone resorption through a PGE2-mediated process in human osseous tissues.
D000328:Adult; D000527:Alprostadil; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism*; D001862:Bone Resorption / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology; D002460:Cell Line; D002648:Child; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost; D015232:Dinoprostone; D066246:ErbB Receptors; D005260:Female; D005870:Giant Cell Tumors / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D012516:Osteosarcoma / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis* / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*
D010281:Parathyroid Hormone; D011458:Prostaglandins E; D011460:Prostaglandins F; D011956:Receptors, Cell Surface; D002116:Calcitonin; D015237:Dinoprost; D000242:Cyclic AMP; D066246:ErbB Receptors; D000527:Alprostadil; D015232:Dinoprostone; D007213:Indomethacin