Hormonal and metabolic regulation of human chondrosarcoma in vitro

Prostaglandin A1 has a profound inhibitory effect on uridine incorporation into RNA of normal cartilage whereas N6-monobutyryladenosine 3',5'-cyclic monophosphate is either stimulatory or without an effect. Sera from intact and growth hormone-treated hypophysectomized rats stimulate RNA synthesis but serum from untreated hypophysectomized rats does not. The present study investigated the in vitro regulation of [3H]uridine incorporation into RNA of six human chondrosarcomas to determine if malignant human chondrocytes are under similar metabolic and hormonal regulation. Prostaglandin A1 (25 micrograms/ml) markedly inhibited uridine incorporation in all six tumors (56 to 80%). N6-Monobutyryladenosine 3',5'-cyclic monophosphate (1 mM) inhibited uridine incorporation in five tumors (20 to 50%). Uridine incorporation was stimulated by growth hormone-dependent serum factors in one tumor and by growth hormone-independent serum factors in two tumors. Two tumors were more responsive to serum from growth hormone-treated hypophysectomized rats than to serum from intact rats, and one tumor was unresponsive to serum stimulation. The data indicate that: (a) prostaglandin A1 is a very potent inhibitor of RNA synthesis in human chondrosarcomas; (b) N6-monobutyryladenosine 3',5'-cyclic monophosphate affects human chondrosarcomas differently than it does normal cartilage; and (c) responses of human chondrosarcomas to serum growth factors vary among individual tumors.