粒细胞巨噬细胞集落刺激因子通过在肿瘤驯化巨噬细胞中启动抗血管生成程序来抑制乳腺癌的生长和转移。
Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages.
作者信息
Eubank Tim D, Roberts Ryan D, Khan Mahmood, Curry Jennifer M, Nuovo Gerard J, Kuppusamy Periannan, Marsh Clay B
机构信息
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.
出版信息
Cancer Res. 2009 Mar 1;69(5):2133-40. doi: 10.1158/0008-5472.CAN-08-1405. Epub 2009 Feb 17.
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.
摘要
肿瘤诱导的巨噬细胞促进肿瘤转移和血管生成。我们发现粒细胞巨噬细胞集落刺激因子（GM-CSF）通过产生可溶性血管内皮生长因子受体-1（sVEGFR-1）来阻断巨噬细胞的血管内皮生长因子（VEGF）活性，并确定其对肿瘤相关巨噬细胞行为和肿瘤生长的影响。我们发现GM-CSF治疗小鼠乳腺肿瘤可减缓肿瘤生长和转移。这些肿瘤中的巨噬细胞更多，血管更少，氧浓度更低。这种作用依赖于sVEGFR-1。原位杂交和流式细胞术确定巨噬细胞是sVEGFR-1的主要来源。这些数据表明，GM-CSF可以重塑巨噬细胞，以减少小鼠乳腺癌中的血管生成和转移。
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