Cytokines in Human Melanoma Cells: Synthesis, Autocrine Stimulation and Regulatory Functions--an Overview

Various cytokines are involved in growth regulation of human melanoma cells. Malignant melanoma cells express multiple growth factors, including basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-alpha, and melanoma growth stimulatory activity (MGSA), substances which are not expressed in normal human melanocytes. The simultaneous synthesis of growth factors and expression of their receptors by melanoma cells, leading to permanent stimulation of cell proliferation, has been clearly shown for bFGF and MGSA. This phenomenon has been designated autocrine growth stimulation. Increased or altered expression of growth factor receptors has been described for nerve growth factor (NGF) receptor, for PDGF-beta receptor and for a truncated form of epidermal growth factor (EGF) receptor encoded by the c-erb-B2 oncogene. Lymphokines are mainly involved in growth control of melanoma cells. Interferons (IFN)-alpha, -beta and -gamma, Interleukins (IL)-1 and -6 as well as tumour necrosis factor (TNF)-alpha inhibited melanoma cell proliferation, with the strongest effects displayed by IFN. TGF-beta which was found to inhibit proliferation of normal human melanocytes exhibited marginal effects on melanoma cells, or even stimulated their growth. In conclusion, a complex network of cytokines is involved in the regulation of melanoma cell growth. Further insight into these mechanisms may contribute to the finding of new strategies in melanoma therapy.