Interactions of melanocytes and melanoma cells with the microenvironment.

Normal or malignant melanocytes interact with the microenvironment through the release of soluble factors from cells and through direct cell-cell contact. Melanoma cells produce a large number of different growth factors and cytokines that affect angiogenesis, stroma formation, motility, and the inflammatory and immune response. Most of the angiogenic growth factors produced by melanoma cells are also mitogenic for fibroblasts. The mechanisms and the receptors involved in direct cell-cell contacts of melanocytes and melanoma cells are largely unknown, but the regulatory role of keratinocytes for melanocytic cells appears at several levels. Keratinocytes induce a dendritic morphology in melanocytes, and control proliferation to maintain a constant keratinocyte/melanocyte ratio during exponential growth. Expression of cell surface adhesion receptors is controlled by keratinocytes on melanocytes and nevus cells but not on advanced melanoma cells. These studies underline the complex interactions between skin cells. The escape of melanocytes from the control by keratinocytes may be a hallmark of nevus cells, and the constitutive production of various growth factors and cytokines appears to represent a major characteristic of melanoma cells.