Adhesion Molecules in Melanoma—More than Just Superglue?

Abstract

Malignant melanoma is increasing in incidence, and, though early lesions are readily treatable, systemic therapy for metastatic disease remains disappointing. Integrins are a family of cell-surface molecules that mediate adhesion between the cell and the extracellular matrix. One member of the integrin family, the αvβ3 integrin, is associated with progression of melanomas, in that the most malignant cells express the highest levels of αvβ3. Like many members of the integrin family, αvβ3 recognizes the sequence Arg-Gly-Asp (RGD) in its ligands, and other molecules that contain this sequence will compete with the natural ligands (such as vitronectin) for binding. There is growing evidence that integrins function as receptors for signal transduction, and that integrin-mediated signalling can affect cell behaviour and even cell survival. Under certain circumstances, loss of integrin-mediated signalling will induce apoptosis, or programmed cell death, and we have demonstrated that melanoma cells treated with a cyclic peptide with high affinity for the αvβ3 integrin will undergo apoptosis within three days. This mechanism might be exploited therapeutically.