Paracrine and autocrine regulation of human melanocyte and melanoma cell growth by transforming growth factor beta in vitro

Anticancer Res. Nov-Dec 1994;14(6B):2565-71.


It has been considered that the growth of human melanoma cells is positively and negatively regulated by transforming growth factors. To investigate further the role of transforming growth factor beta (TGF-beta) in melanoma biology, we analysed paracrine and autocrine growth regulatory properties of TGF-beta in normal human melanocytes and malignant melanoma cell lines in vitro. Exogenously added TGF-beta 1 potently inhibited normal melanocyte proliferation and DNA-synthesis in all cultures examined; in contrast, TGF-beta 1 inhibited only moderately or not at all the growth of cultured melanoma cells. Melanoma cell lines established from metastatic lesions were found to be less sensitive to TGF-beta 1 than those derived from primary melanomas. TGF-beta 1 resistance correlated with high levels of active TGF-beta secreted by metastatic cell lines. Inactivation of endogenously produced TGF-beta by neutralizing anti-TGF-beta antibody resulted in the stimulation of cell proliferation of a TGF-beta-sensitive primary melanoma cell line but not of a resistant metastatic one. These findings suggest that TGF-beta may function as a paracrine and autocrine growth inhibiting factor in the growth regulation of human melanocytic cells. The gradual loss of response of melanocytic cells to TGF-beta during malignant progression suggests that escape of melanoma cells from growth regulation by TGF-beta could be involved in melanoma oncogenesis.

Publication types

  • Comparative Study

MeSH terms

  • Antibodies
  • Cell Division / drug effects*
  • Cell Line
  • DNA / biosynthesis
  • DNA / drug effects
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Kinetics
  • Melanocytes / cytology*
  • Melanocytes / drug effects
  • Melanoma / pathology*
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta / physiology
  • Tumor Cells, Cultured


  • Antibodies
  • DNA, Neoplasm
  • Transforming Growth Factor beta
  • DNA