Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis - PubMed (original) (raw)

doi: 10.1016/j.ccr.2004.11.023.

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

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• PMID: 15652753
• DOI: 10.1016/j.ccr.2004.11.023

Free article

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

Yuval Shaked et al. Cancer Cell. 2005 Jan.

Free article

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.

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Comment in

• A surrogate marker to monitor angiogenesis at last.
  Schneider M, Tjwa M, Carmeliet P. Schneider M, et al. Cancer Cell. 2005 Jan;7(1):3-4. doi: 10.1016/j.ccr.2004.12.014. Cancer Cell. 2005. PMID: 15652744

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