Role of integrins as signal transducing cell adhesion molecules in human cutaneous melanoma

Tumour progression involves a series of sequential steps leading to metastasis. For several of these steps, tumour cells must be equipped with the appropriate adhesive phenotype. Contact with adjacent cells in the primary tumour must be reduced, and invasion and metastasis require adhesive interactions with ECM components. A group of adhesion molecules called integrins is involved in many of these interactions. Integrins are heterodimeric transmembrane molecules that link the cell to the cytoskeleton. They mediate adhesion to ECM components and to other cells. They may be present in an active or inactive conformation, and in addition to adhesive events, they transfer signals into the cell inducing changes in gene expression. Both functions implicate integrins in tumour progression, and their role in cancer has been the subject of many studies over the past 5 years. Several studies of human cutaneous melanoma have demonstrated that the expression of integrins correlates with tumour progression in vivo. Furthermore, integrin expression and function in melanoma cell lines have been found to correlate with invasive or metastatic potential. Finally, evidence from experimental studies in vitro and in vivo shows that integrins have a role in melanoma tumorigenesis, invasion, angiogenesis and metastasis. Integrins might be used as prognostic markers for clinical outcome and they may be useful therapeutic targets in melanoma.