Expression of transforming growth factor-beta (TGF-beta) receptors, TGF-beta 1 and TGF-beta 2 production and autocrine growth control in osteosarcoma cells.
Transforming growth factor-beta (TGF-beta) is a polypeptide with multiple physiological functions. Isoforms of this growth factor have important roles in control of the cell cycle, in regulation of cell-cell interactions and in growth and development. Malignant transformation has been shown to be associated with increased expression of TGF-beta. Since bone is the largest storage site and producer of TGF-beta, we speculated on the existence of an autocrine mechanism in osteosarcoma, a malignant bone tumor. Expression of TGF-beta cell surface receptors, effects on growth of TGF-beta and TGF-beta antibodies and production of 2 TGF-beta isoforms were studied in a panel of 7 osteosarcoma cell lines. In contrast to most previous reports on the effects of TGF-beta on osteosarcoma cell growth, we found a mitogenic effect of TGF-beta 1 in 4 of 7 osteosarcoma cell lines. Receptor profiles for TGF-beta were aberrant in 5 of the 7 cell lines tested, and production of TGF-beta 1 and TGF-beta 2 varied among cell lines. Addition of anti-TGF-beta antagonized the effects of endogenous TGF-beta. Our results suggest a potential role of TGF-beta in autocrine growth control of osteosarcoma cells.
Kloen
P
P
Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Jennings
C L
CL
Gebhardt
M C
MC
Springfield
D S
DS
Mankin
H J
HJ
D000906:Antibodies / Q000494:pharmacology; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D007536:Isomerism; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*; D013268:Stimulation, Chemical; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000906:Antibodies; D003470:Culture Media; D004273:DNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta