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 multi ple physiological functions. Isoforms of this growth factor have impor tant roles in control of the cell cycle, in regulation of cell-cell in teractions and in growth and development. Malignant transformation has been shown to be associated with increased expression of TGF-beta. Si nce bone is the largest storage site and producer of TGF-beta, we spec ulated on the existence of an autocrine mechanism in osteosarcoma, a m alignant bone tumor. Expression of TGF-beta cell surface receptors, ef fects 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 lin es. 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 i n 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 ant agonized the effects of endogenous TGF-beta. Our results suggest a pot ential role of TGF-beta in autocrine growth control of osteosarcoma ce lls. (C) 1994 Wiley-Liss, Inc.