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PMID: 11553709 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular biology of the cell ·Vol. 12 ·No. 9 ·2001-09-00 ·Pages 2699-710

Voura EB, Ramjeesingh RA, Montgomery AM, Siu CH

Abstract

Tumor metastasis involves many stage-specific adhesive interactions. The expression of several cell adhesion molecules, notably the integrin alpha(v)beta(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)beta(3) in the transmigration of melanoma cells through a monolayer of human lung microvascular endothelial cells. Confocal microscopy revealed the presence of the integrin alpha(v)beta(3) on melanoma membrane protrusions and pseudopods penetrating the endothelial junction. alpha(v)beta(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-alpha(v)beta(3) monoclonal antibody LM609. Although both platelet endothelial cell adhesion molecule-1 and L1 are known to bind integrin alpha(v)beta(3), only L1 serves as a potential ligand for alpha(v)beta(3) during melanoma transendothelial migration. Also, polyclonal antibodies against L1 partially inhibited the transendothelial migration of melanoma cells. However, addition of both L1 and alpha(v)beta(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 alpha(v)beta(3) on melanoma cells and L1 on endothelial cells play an important role in the transendothelial migration of melanoma cells.

MeSH Terms
Cell Adhesion/drug effects Cell Movement/drug effects Cells, Cultured Coculture Techniques Endothelium, Vascular/metabolism Gene Deletion Humans Leukocyte L1 Antigen Complex Lung/blood supply Melanoma/genetics,metabolism,pathology Membrane Glycoproteins/metabolism Microscopy, Confocal Neoplasm Metastasis Neural Cell Adhesion Molecules/metabolism Oligopeptides/pharmacology Pseudopodia/metabolism Receptors, Vitronectin/genetics,metabolism Time Factors Tumor Cells, Cultured
Chemicals
Leukocyte L1 Antigen Complex Membrane Glycoproteins Neural Cell Adhesion Molecules Oligopeptides Receptors, Vitronectin arginyl-glycyl-aspartic acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Voura E B
Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada M5G 1L6.
Ramjeesingh R A
Montgomery A M
Siu C H
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.12.9.2699
Published
2001-09-00
Pages
2699-710
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC59705
Subset
IM
Grants
NCI NIH HHS · R01 CA069112 · United States
NCI NIH HHS · CA-69112 · United States
NHLBI NIH HHS · HL-62477 · United States
External Links
PubMed source DOI: 10.1091/mbc.12.9.2699 PMC Full Text View journal details
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