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
-
Gemcitabine
-
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
-
Paclitaxel
-
Gemcitabine