title: Paracrine and autocrine regulation of human melanocyte and melanoma cell growth by transforming growth factor beta in vitro.
abstract: 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.
authors.affiliation: Department of Dermatology, Univ. Medical Center Benjamin Franklin, Free University of Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Krasagakis
authors.forename: C
authors.initials: C
authors.lastname: Garbe
authors.forename: P I
authors.initials: PI
authors.lastname: Schrier
authors.forename: C E
authors.initials: CE
authors.lastname: Orfanos
mesh_terms: D000906:Antibodies; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects; D008545:Melanoma / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D004273:DNA, Neoplasm; D016212:Transforming Growth Factor beta; D004247:DNA