Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration.
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.
Cao
Gaoyuan
G
Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Pennsylvania, Philadelphia, 19104, USA.
O'Brien
Christopher D
CD
Zhou
Zhao
Z
Sanders
Samuel M
SM
Greenbaum
Jordan N
JN
Makrigiannakis
Antonis
A
DeLisser
Horace M
HM
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*
D019408:Platelet Endothelial Cell Adhesion Molecule-1