Modulation of transforming growth factor beta 1 effects on prostate cancer cell proliferation by growth factors and extracellular matrix

Cancer Res. 1995 Jun 15;55(12):2596-602.

Abstract

Poorly differentiated MATLyLu rat prostate cancer cells are resistant to the growth inhibitory effect of transforming growth factor (TGF) beta 1 in vivo, but are inhibited by TGF-beta 1 in vitro. However, TGF-beta 1 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-beta 1 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-beta 1 caused maximum inhibition. In the presence of basic fibroblast growth factor (10 ng/ml), TGF-beta 1 did not inhibit proliferation. In the presence of epidermal growth 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, growth factors, or extracellular matrix to prevent or blunt the growth inhibitory effect of TGF-beta 1 in vitro probably explains why TGF-beta 1 does not inhibit tumor growth in vivo. Thus, prostate cancer cells express high levels of TGF-beta and retain exquisite sensitivity to the growth inhibitory effect of TGF-beta, but have devised a way to protect themselves from growth inhibition by TGF-beta in vivo. TGF-beta 1 stimulated MATLyLu cell motility even at high cell density, suggesting that TGF-beta 1 might affect motility even in vivo and contribute to the aggressiveness of the tumor, without affecting proliferation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma
  • Animals
  • Cell Adhesion / drug effects
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Cell Movement / drug effects*
  • Clone Cells
  • Culture Media
  • Culture Media, Serum-Free
  • Drug Interactions
  • Epidermal Growth Factor / pharmacology*
  • Extracellular Matrix / physiology*
  • Extracellular Matrix Proteins / pharmacology*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Male
  • Prostatic Neoplasms
  • Rats
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Culture Media
  • Culture Media, Serum-Free
  • Extracellular Matrix Proteins
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2
  • Epidermal Growth Factor