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Autocrine Growth Stimulation by Transforming Growth Factor in Asbestos-transformed Rat Mesothelial Cells

Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709

Although the association between asbestos exposure and mesothelioma development has been established for decades, very little is known regarding the molecular mechanism(s) by which asbestos fibers induce this disease. In this series of experiments, the potential for transforming growth factor (TGF-) to act as an autocrine growth factor in transformed mesothelial cells was examined in rats, a model system frequently used to assess the tumorigenic potential of fibrous particulates. Both asbestos-transformed cells and spontaneously transformed cells expressed functional EGF receptors, although only the asbestos-transformed cells expressed TGF-. Expression of TGF- transcripts was correlated with secretion of picogram amounts of growth factor into conditioned medium by the asbestos-transformed cells. In addition, whereas TGF- inhibited the growth of spontaneously transformed mesothelial cells, it stimulated the growth of asbestos-transformed cells. Neutralizing antibody that recognized TGF- secreted by the asbestos-transformed cells was able to inhibit the growth of these cells. Taken together, these data indicate that TGF- acts as an autocrine growth factor for asbestos-transformed rat mesothelial cells. Therefore, in asbestos-transformed mesothelial cells, altered production and responsiveness to TGF- distinguish these cells from spontaneously transformed mesothelial cells. These data suggest that differences in mesothelioma etiology may be reflected in differences in the molecular alterations present in these tumors.

¹ Present Address: Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, P.O. Box 389, Smithville, TX 78957.

² To whom requests for reprints should be addressed.

Received 7/25/94. Accepted 11/22/94.

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