Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells

Citation
Eb. Voura et al., Involvement of integrin alpha(v)beta(3) and cell adhesion molecule L1 in transendothelial migration of melanoma cells, MOL BIOL CE, 12(9), 2001, pp. 2699-2710
Citations number
71
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR BIOLOGY OF THE CELL
ISSN journal
1059-1524 → ACNP
Volume
12
Issue
9
Year of publication
2001
Pages
2699 - 2710
Database
ISI
SICI code
1059-1524(200109)12:9<2699:IOIAAC>2.0.ZU;2-K
Abstract
Tumor metastasis involves many stage-specific adhesive interactions. The ex pression of several cell adhesion molecules, notably the integrin alpha (v) ss (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 alpha (v )ss (3) in the transmigration of melanoma cells through a monolayer of huma n lung microvascular endothelial cells. Confocal microscopy revealed the pr esence of the integrin alpha (v)ss (3) on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. alpha (v)ss (3) was also enriched in heterotypic contacts between endothelial cells and melanoma cel ls. Transendothelial migration of melanoma cells was inhibited by either a cyclic Arg-Gly-Asp peptide or the anti-alpha (v)ss (3) monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 a re known to bind integrin alpha (v)ss (3), only L1 serves as a potential li gand for alpha (v)ss (3) during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial m igration of melanoma cells. However, addition of both L1 and alpha (v)ss (3 ) antibodies did not show additive effects, suggesting that they are compon ents of the same adhesion system. Together, the data suggest that interacti ons between the integrin alpha (v)ss (3) on melanoma cells and L1 on endoth elial cells play an important role in the transendothelial migration of mel anoma cells.