Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis: Implications for cellular surrogate marker analysis of antiangiogenesis

Yuval Shaked, Francesco Bertolini, Shan Man, Michael S. Rogers, Dave Cervi, Thomas Foutz, Kimberley Rawn, Daniel Voskas, Daniel J. Dumont, Yaacov Ben-David, Jack Lawler, Jack Henkin, Jim Huber, Daniel J. Hicklin, Robert J. D'Amato, Robert S. Kerbel*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    329 Scopus citations

    Abstract

    Development of antiangiogenic therapies would be significantly facilitated by quantitative surrogate pharmacodynamic markers. Circulating peripheral blood endothelial cells (CECs) and/or their putative progenitor subset (CEPs) have been proposed but not yet fully validated for this purpose. Herein, we provide such validation by showing a striking correlation between highly genetically heterogeneous bFGF- or VEGF-induced angiogenesis and intrinsic CEC or CEP levels measured by flow cytometry, among eight different inbred mouse strains. Moreover, studies using genetically altered mice showed that levels of these cells are affected by regulators of angiogenesis, including VEGF, Tie-2, and thrombospondin-1. Finally, treatment with a targeted VEGFR-2 antibody caused a dose-dependent reduction in viable CEPs that precisely paralleled its previously and empirically determined antitumor activity.

    Original languageEnglish (US)
    Pages (from-to)101-111
    Number of pages11
    JournalCancer Cell
    Volume7
    Issue number1
    DOIs
    StatePublished - Jan 2005

    ASJC Scopus subject areas

    • Oncology
    • Cell Biology
    • Cancer Research

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