title: Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents.
abstract: 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.
authors.affiliation: Molecular and Cellular Biology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada. yshaked@tx.technion.ac.il
authors.forename: Yuval
authors.initials: Y
authors.lastname: Shaked
authors.forename: Erik
authors.initials: E
authors.lastname: Henke
authors.forename: Jeanine M L
authors.initials: JM
authors.lastname: Roodhart
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancuso
authors.forename: Marlies H G
authors.initials: MH
authors.lastname: Langenberg
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Laura G
authors.initials: LG
authors.lastname: Daenen
authors.forename: Shan
authors.initials: S
authors.lastname: Man
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Urban
authors.initials: U
authors.lastname: Emmenegger
authors.forename: Terence
authors.initials: T
authors.lastname: Tang
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Zhu
authors.forename: Larry
authors.initials: L
authors.lastname: Witte
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.forename: Francesco
authors.initials: F
authors.lastname: Bertolini
authors.forename: Emile E
authors.initials: EE
authors.lastname: Voest
authors.forename: Robert
authors.initials: R
authors.lastname: Benezra
authors.forename: Robert S
authors.initials: RS
authors.lastname: Kerbel
mesh_terms: 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
chemical_list: 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
references.citation: Nat Biotechnol. 2007 Aug;25(8):911-20
references.pmid: 17664940
references.citation: J Biol Chem. 2006 Jan 13;281(2):951-61
references.pmid: 16278208
references.citation: N Engl J Med. 2007 Dec 27;357(26):2666-76
references.pmid: 18160686
references.citation: PLoS One. 2007 Dec 19;2(12):e1338
references.pmid: 18092003
references.citation: FASEB J. 2006 Jan;20(1):95-102
references.pmid: 16394272
references.citation: Arterioscler Thromb Vasc Biol. 2008 Feb;28(2):217-22
references.pmid: 18096826
references.citation: Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):296-301
references.pmid: 15569821
references.citation: Science. 2006 May 26;312(5777):1171-5
references.pmid: 16728631
references.citation: Circulation. 2003 Nov 18;108(20):2491-7
references.pmid: 14581398
references.citation: Nature. 1999 Oct 14;401(6754):670-7
references.pmid: 10537105
references.citation: Nat Rev Cancer. 2004 Jun;4(6):423-36
references.pmid: 15170445
references.citation: Cancer Res. 2006 Apr 1;66(7):3639-48
references.pmid: 16585189
references.citation: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6620-5
references.pmid: 18443294
references.citation: Cancer Cell. 2005 Sep;8(3):211-26
references.pmid: 16169466
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17069-74
references.pmid: 17942672
references.citation: Science. 2006 Sep 22;313(5794):1785-7
references.pmid: 16990548
references.citation: N Engl J Med. 2006 Dec 14;355(24):2542-50
references.pmid: 17167137
references.citation: N Engl J Med. 2004 Jun 3;350(23):2335-42
references.pmid: 15175435
references.citation: Nat Med. 2005 Mar;11(3):261-2
references.pmid: 15723071
references.citation: Cancer Cell. 2004 Dec;6(6):553-63
references.pmid: 15607960
references.citation: J Clin Oncol. 2006 Apr 1;24(10):1491-8
references.pmid: 16574998
references.citation: Oncologist. 2008 Mar;13(3):289-98
references.pmid: 18378539
references.citation: Blood. 2005 Nov 1;106(9):3058-61
references.pmid: 15998832
references.citation: Nat Med. 2006 May;12(5):557-67
references.pmid: 16648859
references.citation: J Clin Oncol. 2001 Feb 15;19(4):1195-206
references.pmid: 11181686
references.citation: Science. 2005 Jan 7;307(5706):58-62
references.pmid: 15637262
references.citation: J Clin Invest. 2000 Apr;105(8):R15-24
references.pmid: 10772661
references.citation: Nat Rev Cancer. 2006 Nov;6(11):835-45
references.pmid: 17036040
references.citation: Circulation. 2003 Mar 11;107(9):1322-8
references.pmid: 12628955
references.citation: Cancer Res. 1999 Oct 15;59(20):5209-18
references.pmid: 10537299
references.citation: Nat Med. 2004 Jan;10(1):64-71
references.pmid: 14702636
references.citation: Cancer Cell. 2005 Jan;7(1):101-11
references.pmid: 15652753
references.citation: Br J Cancer. 2006 Feb 27;94(4):524-31
references.pmid: 16450002
references.citation: Circ Res. 2004 Aug 20;95(4):343-53
references.pmid: 15321944
references.citation: Cell. 2006 Jan 13;124(1):175-89
references.pmid: 16413490
references.citation: N Engl J Med. 2008 May 8;358(19):2039-49
references.pmid: 18463380
references.citation: Br J Cancer. 2002 Jul 29;87(3):344-7
references.pmid: 12177806
references.citation: J Reprod Immunol. 2001 May;50(2):105-19
references.pmid: 11334993
references.citation: Cancer Res. 2003 Aug 1;63(15):4342-6
references.pmid: 12907602
references.citation: J Clin Oncol. 1999 Jul;17(7):2190-7
references.pmid: 10561275
references.citation: Ann Oncol. 2007 Aug;18(8):1421-2
references.pmid: 17693656
references.citation: Hum Gene Ther. 2000 Jan 20;11(2):247-61
references.pmid: 10680839
references.citation: Cancer Res. 2000 Apr 1;60(7):1878-86
references.pmid: 10766175
references.citation: Am J Respir Crit Care Med. 2003 Jun 15;167(12):1676-86
references.pmid: 12626353
references.citation: Oncology (Williston Park). 2005 Apr;19(4 Suppl 3):26-31
references.pmid: 15934500
references.citation: EMBO J. 1999 Jul 15;18(14):3964-72
references.pmid: 10406801