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          Institute: MPI für molekulare Biomedizin     Collection: Publikationen molekulare Biomedizin     Display Documents



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ID: 123170.0, MPI für molekulare Biomedizin / Publikationen molekulare Biomedizin
Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis
Authors:Vajkoczy, P.; Blum, S.; Lamparter, M.; Mailhammer, R.; Erber, R.; Engelhardt, B.; Vestweber, D.; Hatzopoulos, A. K.
Language:English
Date of Publication (YYYY-MM-DD):2003-06-16
Title of Journal:Journal of Experimental Medicine
Journal Abbrev.:J Exp Med
Volume:197
Issue / Number:12
Start Page:1755
End Page:1765
Review Status:not specified
Audience:Not Specified
Abstract / Description:Tissue neovascularization involves recruitment of circulating endothelial progenitor cells that originate in the bone marrow. Here, we show that a class of embryonic endothelial progenitor cells (Tie-2+, c-Kit+, Sca-1+, and Flk-1-/low), which were isolated at E7.5 of mouse development at the onset of vasculogenesis, retain their ability to contribute to tumor angiogenesis in the adult. Using intravital fluorescence videomicroscopy, we further defined the multistep process of embryonic endothelial progenitor cell (eEPC) homing and incorporation. Circulating eEPCs are specifically arrested in "hot spots" within the tumor microvasculature, extravasate into the interstitium, form multicellular clusters, and incorporate into functional vascular networks. Expression analysis and in vivo blocking experiments provide evidence that the initial cell arrest of eEPC homing is mediated by E- and P-selectin and P-selectin glycoprotein ligand 1. This paper provides the first in vivo insights into the mechanisms of endothelial progenitor cell recruitment and, thus, indicates novel ways to interfere with pathological neovascularization.
Free Keywords:Animals
; Antigens, CD31/metabolism
; Biological Markers
; Blood Vessels/cytology/metabolism
; Cell Adhesion/physiology
; Embryo
; Endothelium, Vascular/*cytology/embryology/metabolism
; Glioma/*blood supply/metabolism/pathology
; Hemodynamic Processes
; Membrane Glycoproteins/metabolism
; Mice
; *Neovascularization, Pathologic
; Selectins/metabolism
; Stem Cells/*physiology
; Support, Non-U.S. Gov't
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für molekulare Biomedizin
Identifiers:URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=... [ID No:1]
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