Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization Journal Article

   


Authors: Nolan, D. J.; Ciarrocchi, A.; Mellick, A. S.; Jaggi, J. S.; Bambino, K.; Gupta, S.; Heikamp, E.; McDevitt, M. R.; Scheinberg, D. A.; Benezra, R.; Mittal, V.
Article Title: Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization
Abstract: Tumors build vessels by cooption of pre-existing vasculature and de novo recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry. We show that early tumors recruit BM-derived EPCs that differentiate into mature BM-derived endothelial cells (ECs) and luminally incorporate into a subset of sprouting tumor neovessels. Notably, in later tumors, these BM-derived vessels are diluted with non-BM-derived vessels from the periphery, which accounts for purported differences in previously published reports. Furthermore, we show that specific ablation of BM-derived EPCs with α-particle-emitting anti-VE-cadherin antibody markedly impaired tumor growth associated with reduced vascularization. Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis. © 2007 by Cold Spring Harbor Laboratory Press.
Keywords: microscopy; flow cytometry; animals; mice; bone marrow; tumor differentiation; in vivo study; cell differentiation; cell line, tumor; neovascularization, pathologic; mice, inbred c57bl; mice, transgenic; stem cell; endothelium cell; endothelial cells; breast tumor; hematopoietic stem cells; neoplasms, experimental; tumor growth; bone marrow transplantation; neovascularization; tumor vascularization; neovascularization (pathology); genetic marker; mammary neoplasms, experimental; tumor angiogenesis; ve-cadherin; endothelial progenitor cells
Journal Title: Genes and Development
Volume: 21
Issue: 12
ISSN: 0890-9369
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2007-06-15
Start Page: 1546
End Page: 1558
Language: English
DOI: 10.1101/gad.436307
PUBMED: 17575055
PROVIDER: scopus
PMCID: PMC1891431
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-34250719709&partnerID=40&md5=19742e1a0089f6b2f386b80172cf4615
Notes: --- - "Cited By (since 1996): 118" - "Export Date: 17 November 2011" - "CODEN: GEDEE" - "Source: Scopus"
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MSK Authors
  1. Jaspreet Jaggi
    21 Jaggi
  2. Michael R Mcdevitt
    144 Mcdevitt
  3. David Scheinberg
    499 Scheinberg
  4. Robert Benezra
    146 Benezra
  5. Alessia Ciarrocchi
    7 Ciarrocchi
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