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Articles in PresS, published online ahead of print January 9, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00524.2001
Submitted on November 1, 2001
Accepted on January 2, 2002
1 Medicine, University of Pennsylvania, Philadelphia, PA, USA
2 Centocor, Malvern, PA, USA
3 University of Crete, Heraklion, Crete, Greece
* To whom correspondence should be addressed. E-mail: delisser{at}mail.med.upenn.edu.
Platelet endothelial cell adhesion molecule (PECAM-1) has been implicated in angiogenesis, but a number of issues remain unsettled including the independent involvement of human PECAM-1 (huPECAM-1) in tumor angiogenesis and the mechanisms of its participation in vessel formation. We report for tumors grown in human skin transplanted on SCID mice, that antibodies against huPECAM-1 (without simultaneous treatment with anti-VE-cadherin antibody) decreased the density of human, but not murine vessels associated with the tumors. Anti-huPECAM-1 antibody also inhibited tube formation by human umbilical vein endothelial cells (HUVEC) and the migration of HUVEC through Matrigel coated filters or during the repair of wounded cell monolayers. The involvement of huPECAM-1 in these processes was confirmed by the finding that expression of huPECAM-1 in cellular transfectants induced tube formation and enhanced cell motility. These data provide evidence of a role for PECAM-1 in human tumor angiogenesis (independent of VE-cadherin) and suggest that during angiogenesis PECAM-1 participates in adhesive and/or signaling phenomena required for the motility of EC and/or their subsequent organization into vascular tubes.
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