MODULATION OF TRANSFORMING GROWTH-FACTOR-BETA-1 EFFECTS ON PROSTATE-CANCER CELL-PROLIFERATION BY GROWTH-FACTORS AND EXTRACELLULAR-MATRIX

Poorly differentiated MATLyLu rat prostate cancer cells are resistant to the growth inhibitory effect of transforming growth factor (TGF) be ta 1 in vivo, but are inhibited by TGF-beta 1 in vitro. However, TGF-b eta 1 inhibited proliferation only when the cells were plated at low d ensity in serum-free medium (concentration for 50% of maximum inhibiti on, 0.1 ng/ml). TGF-beta 1 was not growth inhibitory when cells were p lated at high density, or at low density in 0.5% serum. At low cell de nsity in serum-free medium, 0.5 ng/ml TGF-beta 1 caused maximum inhibi tion. In the presence of basic fibroblast growth factor (10 ng/ml), TG F-beta 1 did not inhibit proliferation. In the presence of epidermal g rowth factor (50 ng/ml), TGF-beta 1 inhibited proliferation by only 18 %. Growth inhibition by TGF-beta 1 was less effective on extracellular matrix than on plastic The ability of high cell density, serum, growt h factors, or extracellular matrix to prevent or blunt the growth inhi bitory effect of TGF-beta 1 in vitro probably explains why TGF-beta 1 does not inhibit tumor growth in vivo. Thus, prostate cancer cells exp ress high levels of TGF-beta and retain exquisite sensitivity to the g rowth inhibitory effect of TGF-beta, but have devised a way to protect themselves from growth inhibition by TGF-beta in vivo. TGF-beta 1 sti mulated MATLyLu cell motility even at high cell density, suggesting th at TGF-beta 1 might affect motility even in vivo and contribute to the aggressiveness of the tumor, without affecting proliferation.