Expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during melanoma-induced angiogenesis in vivo.
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 alpha 6 laminin receptor, vessels within melanomas showed apparently diminished expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Berger
R
R
Duhring Laboratory for Dermatologic Research, University of Pennsylvania, Philadelphia 19104.
Albelda
S M
SM
Berd
D
D
Ioffreda
M
M
Whitaker
D
D
Murphy
G F
GF
D000328:Adult; D000368:Aged; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000150:complications* / Q000556:secondary; D008562:Membrane Glycoproteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012016:Reference Values; D012878:Skin Neoplasms / Q000098:blood supply / Q000150:complications* / Q000556:secondary
D015214:Antigens, Differentiation, Myelomonocytic; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1