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

• DOI: 10.1152/ajpcell.00524.2001
• Publication Date: 2013-05-14T00:08:22Z
• Authors: Gaoyuan Cao; Christopher D. O'...; Zhao Zhou; Samuel M. Sanders; Jordan N. Greenbaum; Antonis Makrigian...; Horace M. DeLisser
• Keywords: 0301 basic medicine; Neovascularization, Pathologic; Neovascularization, Physiologic; Mice, SCID; In Vitro Techniques; Cell Line; 3. Good health; Platelet Endothelial Cell Adhesion Molecule-1; Mice; 03 medical and health sciences; Cell Movement; Neoplasms; Animals; Blood Vessels; Humans; Endothelium, Vascular

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 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 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 endothelial cells and/or their subsequent organization into vascular tubes.