Abstract
Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that granulocyte macrophage colony-stimulating factor (GM-CSF) blocked macrophages vascular endothelial growth factor (VEGF) activity by producing soluble VEGF receptor-1 (sVEGFR-1) and determined the effect on tumor-associated macrophage behavior and tumor growth. We show GM-CSF treatment of murine mammary tumors slowed tumor growth and slowed metastasis. These tumors had more macrophages, fewer blood vessels, and lower oxygen concentrations. This effect was sVEGFR-1 dependent. In situ hybridization and flow cytometry identified macrophages as the primary source of sVEGFR-1. These data suggest that GM-CSF can re-educate macrophages to reduce angiogenesis and metastases in murine breast cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Angiogenesis Inhibitors / pharmacology*
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Animals
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Apoptosis / drug effects
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Cell Polarity / drug effects
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
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Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
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Lung Neoplasms / prevention & control
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Lung Neoplasms / secondary
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Macrophages / drug effects*
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Macrophages / physiology
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Mammary Neoplasms, Experimental / blood supply
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Mammary Neoplasms, Experimental / drug therapy*
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Mammary Neoplasms, Experimental / pathology
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Mice
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Neutrophils / drug effects
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Oxygen / analysis
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Vascular Endothelial Growth Factor A / analysis
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Vascular Endothelial Growth Factor Receptor-1 / genetics
Substances
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Angiogenesis Inhibitors
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Vascular Endothelial Growth Factor A
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Granulocyte-Macrophage Colony-Stimulating Factor
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Vascular Endothelial Growth Factor Receptor-1
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Oxygen