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Hormonal and Metabolic Regulation of Human Chondrosarcoma in Vitro¹

Departments of Medicine [W. D. M. and H. E. L.], Orthopaedic Surgery [J. M. H.], and Physiology [H. E. L.], Duke University Medical Center, Durham, North Carolina 27710

³ To whom requests for reprints should be addressed, at: Box 21, Downstate Medical Center, 450 Clarkson Ave, Brooklyn, N. Y. 11203.

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 µg/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 thah 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.

¹ This work was supported by a grant from the National Institute of Arthritis, Metabolic and Digestive Diseases (AM01324).

² Present address: Department of Physiology, Marshall University School of Medicine, Huntington, W. V. 25701.

Received 4/ 7/82. Accepted 11/ 5/82.