Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages.
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.
Eubank
Tim D
TD
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Internal Medicine, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio 43210, USA.
Roberts
Ryan D
RD
Khan
Mahmood
M
Curry
Jennifer M
JM
Nuovo
Gerard J
GJ
Kuppusamy
Periannan
P
Marsh
Clay B
CB
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D010100:Oxygen / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D010100:Oxygen