HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/C701    most recent 00245.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Liang, S. Articles by Dong, C. Search for Related Content PubMed PubMed Citation Articles by Liang, S. Articles by Dong, C.

EXTRACELLULAR MATRIX, CELL INTERACTIONS

Integrin VLA-4 enhances sialyl-Lewis^x/a-negative melanoma adhesion to and extravasation through the endothelium under low flow conditions

Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania

Submitted 7 May 2008 ; accepted in final form 11 July 2008

During their passage through the circulatory system, tumor cells undergo extensive interactions with various host cells including endothelial cells. The capacity of tumor cells to form metastasis is related to their ability to interact with and extravasate through endothelial cell layers, which involves multiple adhesive interactions between tumor cells and endothelium (EC). Thus it is essential to identify the adhesive receptors on the endothelial and melanoma surface that mediate those specific adhesive interactions. P-selectin and E-selectin have been reported as adhesion molecules that mediate the cell-cell interaction of endothelial cells and melanoma cells. However, not all melanoma cells express ligands for selectins. In this study, we elucidated the molecular constituents involved in the endothelial adhesion and extravasation of sialyl-Lewis^x/a-negative melanoma cell lines under flow in the presence and absence of polymorphonuclear neutrophils (PMNs). Results show the interactions of ₄β₁ (VLA-4) on sialyl-Lewis^x/a-negative melanoma cells and vascular adhesion molecule (VCAM-1) on inflamed EC supported melanoma adhesion to and subsequent extravasation through the EC in low shear flow. These findings provide clear evidence for a direct role of the VLA-4/VCAM-1 pathway in melanoma cell adhesion to and extravasation through the vascular endothelium in a shear flow. PMNs facilitated melanoma cell extravasation under both low and high shear conditions via the involvement of distinct molecular mechanisms. In the low shear regime, β₂-integrins were sufficient to enhance melanoma cell extravasation, whereas in the high shear regime, selectin ligands and β₂-integrins on PMNs were necessary for facilitating the melanoma extravasation process.

tumor cell extravasation; vascular adhesion molecule-1; leukocytes; inflammation