Expression of platelet‐endothelial cell adhesion molecule‐1 (PECAM‐1) during melanoma‐induced angiogenesis in vivo

Randy Berger, Steven M. Albelda, David Berd, Michael Ioffreda, Diana Whitaker, George F. Murphy

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Recent ultrastructural data indicate that tumor‐induced angiogenesis involves polarized outgrowth of endothelial cells from established vessels into tumor parenchyma and interstitium. Efforts to define the cytoarchitecture of the angiogenic response and to ascertain molecular determinants of polarized endothelial migration have been impeded by lack of sensitive and specific immunologic markers for endothelium and vessel wall components. In this study, we utilized monoclonal antibody to platelet‐endothelial cell adhesion molecule‐1 (PECAM‐1), a cell‐cell adhesion molecule belonging to the immunoglobulin superfamily, to determine extent and patterns of angiogenesis in metastatic melanomas before (N = 7) and after (N = 3) induction of tumor‐infiltrating lymphocyte responses provoked by administration of experimental melanoma vaccine. PECAM‐1 proved to be a more reliable marker for angiogenesis than antibodies to von Willebrand Factor. Although both normal and tumor vessels exhibited prominent staining for PECAM‐1, different patterns of endothelial reactivity were observed. Formation of new vessels was associated with i) PECAM‐1 redistribution from a constitutive circumferential membrane pattern to a pattern restricted to cell‐cell junctions; ii) formation of endothelial cords formed by cell‐cell interactions; and iii) eventual development of open lumens. Vessels within inflamed (vaccine‐treated) and non‐inflamed melanomas did not differ with regard to patterns of PECAM‐1 expression. Forming vessels of inflamed melanomas failed to express the cytokine‐inducible activation marker, E‐selectin. Although normal microvessels and reactive vessels of healing wounds demonstrated prominent staining for α6; laminin receptor, vessels within melanomas showed apparently diminished expression. These data establish PECAM‐1 as a sensitive and specific marker for experimental angiogenesis, and further support the possibility that cell‐cell adhesion mediated by PECAM‐1 may contribute to directed endothelial migration typical of tumor‐induced formation of new vessels.

Original languageEnglish (US)
Pages (from-to)399-406
Number of pages8
JournalJournal of Cutaneous Pathology
Volume20
Issue number5
DOIs
StatePublished - Oct 1993

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Dermatology

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