ADHESION MOLECULES IN MELANOMA - MORE THAN JUST SUPERGLUE

Malignant melanoma is increasing in incidence, and, though early lesio ns are readily treatable, systemic therapy for metastatic disease rema ins disappointing. Integrins are a family of cell-surface molecules th at mediate adhesion between the cell and the extracellular matrix. One member of the integrin family, the alpha v beta 3 integrin, is associ ated with progression of melanomas, in that the most malignant cells e xpress the highest levels of alpha v beta 3. Like many members of the integrin family, alpha v beta 3 recognizes the sequence Arg-Gly-Asp (R GD) in its ligands, and other molecules that contain this sequence wil l compete with the natural ligands (such as vitronectin) for binding. There is growing evidence that integrins function as receptors for sig nal transduction, and that integrin-mediated signalling can affect cel l behaviour and even cell survival. Under certain circumstances, loss of integrin-mediated signalling will induce apoptosis, or programmed c ell death, and we have demonstrated that melanoma cells treated with a cyclic peptide with high affinity for the alpha v beta 3 integrin wil l undergo apoptosis within three days. This mechanism might be exploit ed therapeutically.