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Science 22 September 2006:
Vol. 313. no. 5794, pp. 1785 - 1787
DOI: 10.1126/science.1127592
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Reports

Therapy-Induced Acute Recruitment of Circulating Endothelial Progenitor Cells to Tumors

Yuval Shaked,1* Alessia Ciarrocchi,2* Marcela Franco,1 Christina R. Lee,1 Shan Man,1 Alison M. Cheung,3 Daniel J. Hicklin,4 David Chaplin,5 F. Stuart Foster,3 Robert Benezra,2 Robert S. Kerbel1{dagger}

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. These findings also provide a mechanistic rationale for the enhanced efficacy of VDAs when combined with antiangiogenic drugs.

1 Department of Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.
2 Program of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
3 Department of Imaging Research, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.
4 ImClone Systems, 180 Varick Street, 7th Floor, New York, NY 10014, USA.
5 OXiGENE Inc., 230 Third Avenue, Waltham, MA 02451, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: robert.kerbel{at}sri.utoronto.ca

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Science. ISSN 0036-8075 (print), 1095-9203 (online)