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Modulation of Transforming Growth Factor ß1 Effects on Prostate Cancer Cell Proliferation by Growth Factors and Extracellular Matrix¹

Department of Urology, The Johns Hopkins University School of Medicine, and The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland 21287-2101

Poorly differentiated MATLyLu rat prostate cancer cells are resistant to the growth inhibitory effect of transforming growth factor (TGF) ß1 in vivo, but are inhibited by TGF-ß1 in vitro. However, TGF-ß1 inhibited proliferation only when the cells were plated at low density in serum-free medium (concentration for 50% of maximum inhibition, 0.1 ng/ml). TGF-ß1 was not growth inhibitory when cells were plated at high density, or at low density in 0.5% serum. At low cell density in serum-free medium, 0.5 ng/ml TGF-ß1 caused maximum inhibition. In the presence of basic fibroblast growth factor (10 ng/ml), TGF-ß1 did not inhibit proliferation. In the presence of epidermal growth factor (50 ng/ml), TGF-ß1 inhibited proliferation by only 18%. Growth inhibition by TGF-ß1 was less effective on extracellular matrix than on plastic. The ability of high cell density, serum, growth factors, or extracellular matrix to prevent or blunt the growth inhibitory effect of TGF-ß1 in vitro probably explains why TGF-ß1 does not inhibit tumor growth in vivo. Thus, prostate cancer cells express high levels of TGF-ß and retain exquisite sensitivity to the growth inhibitory effect of TGF-ß, but have devised a way to protect themselves from growth inhibition by TGF-ß in vivo. TGF-ß1 stimulated MATLyLu cell motility even at high cell density, suggesting that TGF-ß1 might affect motility even in vivo and contribute to the aggressiveness of the tumor, without affecting proliferation.

¹ This work was supported by National Cancer Institute Grant CA16924. D. M. M. was supported in part by NICHD Training Grant T32 HD07276.

² To whom requests for reprints should be addressed, at The Johns Hopkins Hospital, Marburg 115, 600 North Wolfe Street, Baltimore, MD 21287-2101.

Received 1/31/95. Accepted 4/19/95.

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