[Frontiers in Bioscience 3, d1005-1010, September 15, 1998] |
MOLECULAR EVENTS IN MELANOMA DEVELOPMENT AND PROGRESSION
Friedegund Meier1, Kapaettu Satyamoorthy1, Mark Nesbit1, Mei-Yu Hsu1, Birgit Schittek2, Claus Garbe2, and Meenhard Herlyn1
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 191041, Department of Dermatology, University of Tuebingen, Liebermeisterstr.25, 72076 Tuebingen, Germany2
Received 7/17/98 Accepted 8/10/98
6. GROWTH FACTORS, CYTOKINES AND THEIR RECEPTORS IN MELANOMA DEVELOPMENT AND PROGRESSION
Melanoma cells express a variety of growth factors and cytokines (figure 7) and their receptors (figure 8) (11). For several years, we have delineated their functions and have distinguished between autocrine growth factors, those involved in stroma induction (including angiogenesis), and those interacting with the host defense system [i.e., with specific T cells and non-specific inflammatory cells (23, 24)]. In a series of experiments, we have evaluated the role of these molecules in angiogenesis, matrix induction, and monocyte and granulocyte attraction (25-27). Growth factors and cytokines are also suitable as progression markers (figure 9). Tumor cells produce growth factors not only for autocrine growth stimulation, but also for paracrine stimulation of the stromal cells (figure 10). Fibroblasts are activated by melanoma-derived PDGF, whereas endothelial cells are activated by VEGF.
Figure 8. Growth factor receptors expressed by melanoma cells. Melanoma cells express receptors at levels from a few hundred sites (MSH-R), to ten-thousand (EGF-R) or hundred-thousand (NGF-R) per cell.
Figure 10. Hypothetical tumor-stroma interactions. Melanoma cells produce bFGF for autocrine growth stimulation. Melanoma-derived PDGF and VEGF activate fibroblasts and stimulate angiogenesis, respectively. The activated stromal cells then provide feedback to the tumor cells by producing their own growth factors.