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

    Author(s)
    Nolan, Daniel J.
    Ciarrocchi, Alessia
    Mellick, Albert S.
    Jaggi, Jaspreet S.
    Bambino, Kathryn
    Gupta, Sunita
    Heikamp, Emily
    McDevitt, Michael R.
    Scheinberg, David A.
    Benezra, Robert
    Mittal, Vivek
    Griffith University Author(s)
    Mellick, Albert S.
    Year published
    2007
    Metadata
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    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 ...
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    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 -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.
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    Journal Title
    Genes & Development
    Volume
    21
    Issue
    12
    Publisher URI
    http://genesdev.cshlp.org/
    DOI
    https://doi.org/10.1101/gad.436307
    Subject
    Cancer Genetics
    Biological Sciences
    Medical and Health Sciences
    Psychology and Cognitive Sciences
    Publication URI
    http://hdl.handle.net/10072/21851
    Collection
    • Journal articles

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