Involvement of Integrin αvβ3and Cell Adhesion Molecule L1 in Transendothelial Migration of Melanoma Cells

Abstract

Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin α v β 3, has been associated with the metastatic potential of tumor cells. In this study, we used a novel in vitro assay to examine the role of α v β 3 in the transmigration of melanoma cells through a monolayer of human lung microvascular endothelial cells. Confocal microscopy revealed the presence of the integrin α v β 3 on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. α v β 3 was also enriched in heterotypic contacts between endothelial cells and melanoma cells. Transendothelial migration of melanoma cells was inhibited by either a cyclic Arg-Gly-Asp peptide or the anti-α v β 3 monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 are known to bind integrin α v β 3, only L1 serves as a potential ligand for α v β 3 during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells. However, addition of both L1 and α v β 3 antibodies did not show additive effects, suggesting that they are components of the same adhesion system. Together, the data suggest that interactions between the integrin α v β 3 on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.