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Granulocyte Macrophage Colony-Stimulating Factor Inhibits Breast Cancer Growth and Metastasis by Invoking an Anti-Angiogenic Program in Tumor-Educated Macrophages

¹ Integrated Biomedical Science Graduate Program, College of Medicine and Public Health, ² Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Internal Medicine, ³ Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, and ⁴ Comprehensive Cancer Center, Department of Pathology, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio

Requests for reprints: Clay B. Marsh, The Ohio State University, 473 West 12th Avenue, 201 DHLRI, Columbus, OH 43210. Phone: 614-293-9309; Fax: 614-688-4662; E-mail: Clay.Marsh{at}osumc.edu.

Key Words: GM-CSF • macrophages • sVEGFR-1

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. [Cancer Res 2009;69(5):2133–40]