Therapy-induced acute recruitment of circulating endothelial progenitor cells to tumors.
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.
Shaked
Yuval
Y
Department of Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.
Ciarrocchi
Alessia
A
Franco
Marcela
M
Lee
Christina R
CR
Man
Shan
S
Cheung
Alison M
AM
Hicklin
Daniel J
DJ
Chaplin
David
D
Foster
F Stuart
FS
Benezra
Robert
R
Kerbel
Robert S
RS
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D011756:Diphosphates / Q000627:therapeutic use; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009336:Necrosis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic; D013234:Stem Cells / Q000502:physiology*; D013267:Stilbenes / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; C511761:DC101 monoclonal antibody; D011756:Diphosphates; C465018:Oxi 4503; D013267:Stilbenes; C058728:fosbretabulin