Rapid chemotherapy-induced acute endothelial progenitor cell mobilization: implications for antiangiogenic drugs as chemosensitizing agents

Cancer Cell. 2008 Sep 9;14(3):263-73. doi: 10.1016/j.ccr.2008.08.001.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / pathology
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Carcinoma, Lewis Lung / blood
  • Carcinoma, Lewis Lung / drug therapy
  • Carcinoma, Lewis Lung / pathology
  • Cell Proliferation / drug effects
  • Chemokine CXCL12 / blood
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Drug Therapy, Combination
  • Endothelial Cells / drug effects*
  • Endothelial Cells / pathology
  • Female
  • Humans
  • Melanoma, Experimental / blood
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasms / blood
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Stem Cells / drug effects*
  • Stem Cells / pathology
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Chemokine CXCL12
  • DC101 monoclonal antibody
  • Vascular Endothelial Growth Factor A
  • Deoxycytidine
  • gemcitabine
  • Paclitaxel