Therapy-Induced Acute Recruitment of Circulating Endothelial Progenitor Cells to Tumors
Shaked Y, Ciarrocchi A, Franco M, Lee CR, Man S, Cheung AM, Hicklin DJ, Chaplin D, Foster FS, Benezra R, Kerbel RS.
Department of Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, Toronto
SCIENCE VOL 313 22 SEPTEMBER 2006, PP. 1785 – 1787.

• > The contribution of bone marrow–derived circulating endothelial progenitor cells (CEPs) to tumor angiogenesis has been controversial, primarily because of their low numbers in blood vessels of untreated tumors. We show that treatment of tumor-bearing mice with vascular disrupting agents (VDAs) leads to an acute mobilization of CEPs, which home to the viable tumor rim that characteristically remains after such therapy. Disruption of this CEP spike by antiangiogenic drugs or by genetic manipulation resulted in marked reductions in tumor rim size and blood flow as well as enhanced VDA antitumor activity. Longitudinal measurement of blood flow within the tumors were measured nsuiing high-frequency micro-ultrasound (Vevo 660, VisualSonics). These findings also provide a mechanistic rationale for the enhanced efficacy of VDAs when combined with antiangiogenic drugs.