Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration

Platelet endothelialcell adhesion molecule (PECAM)-1 has been implicated inangiogenesis, but a number of issues remain unsettled, including theindependent involvement of human PECAM-1 (huPECAM-1) in tumorangiogenesis and the mechanisms of its participation in vesselformation. We report for tumors grown in human skin transplanted on severe combined immunodeficiency 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 alsoinhibited 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 ofhuPECAM-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 arole for PECAM-1 in human tumor angiogenesis (independent ofVE-cadherin) and suggest that during angiogenesis PECAM-1 participates in adhesive and/or signaling phenomena required for the motility ofendothelial cells and/or their subsequent organization into vascular tubes.