Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents.
Several hypotheses have been proposed to explain how antiangiogenic drugs enhance the treatment efficacy of cytotoxic chemotherapy, including impairing the ability of chemotherapy-responsive tumors to regrow after therapy. With respect to the latter, we show that certain chemotherapy drugs, e.g., paclitaxel, can rapidly induce proangiogenic bone marrow-derived circulating endothelial progenitor (CEP) mobilization and subsequent tumor homing, whereas others, e.g., gemcitabine, do not. Acute CEP mobilization was mediated, at least in part, by systemic induction of SDF-1alpha and could be prevented by various procedures such as treatment with anti-VEGFR2 blocking antibodies or paclitaxel treatment in CEP-deficient Id mutant mice, both of which resulted in enhanced antitumor effects mediated by paclitaxel, but not by gemcitabine.
Shaked
Yuval
Y
Molecular and Cellular Biology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada. yshaked@tx.technion.ac.il
Henke
Erik
E
Roodhart
Jeanine M L
JM
Mancuso
Patrizia
P
Langenberg
Marlies H G
MH
Colleoni
Marco
M
Daenen
Laura G
LG
Man
Shan
S
Xu
Ping
P
Emmenegger
Urban
U
Tang
Terence
T
Zhu
Zhenping
Z
Witte
Larry
L
Strieter
Robert M
RM
Bertolini
Francesco
F
Voest
Emile E
EE
Benezra
Robert
R
Kerbel
Robert S
RS
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008546:Melanoma, Experimental / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D054377:Chemokine CXCL12; C511761:DC101 monoclonal antibody; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine
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