Author/Authors :
Shaked، نويسنده , , Yuval and Bertolini، نويسنده , , Francesco and Man، نويسنده , , Shan and Rogers، نويسنده , , Michael S. and Cervi، نويسنده , , Dave and Foutz، نويسنده , , Thomas and Rawn، نويسنده , , Kimberley and Voskas، نويسنده , , Daniel J. Dumont، نويسنده , , Daniel J. and Ben-David، نويسنده , , Yaacov and Lawler، نويسنده , , Jack and Henkin، نويسنده , , Jack and Huber، نويسنده , , Jim and Hicklin، نويسنده , , Daniel J. and DʹAmato، نويسنده , , Robert J. and Kerbel، نويسنده , , Robert S.، نويسنده ,
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.
