Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages.
Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages.
复制标题
DOI：
10.1158/0008-5472.can-08-1405
复制
发表时间：
2009-03-01
期刊：
影响因子：
11.2
通讯作者：
Marsh CB
中科院分区：
文献类型：
--
作者：
Eubank TD;Roberts RD;Khan M;Curry JM;Nuovo GJ;Kuppusamy P;Marsh CB
受肿瘤训练的巨噬细胞促进肿瘤转移和血管生成。我们发现GM-CSF通过产生可溶性VEGF受体-1（sVEGFR-1）阻断巨噬细胞VEGF活性，并确定了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治疗小鼠乳腺肿瘤减缓了肿瘤生长和转移。这些肿瘤有更多的巨噬细胞，更少的血管和更低的氧气浓度。这种作用是sVEGFR-1依赖性的。原位杂交和流式细胞术鉴定巨噬细胞为sVEGFR-1的主要来源。这些数据表明，GM-CSF可以再教育巨噬细胞，以减少小鼠乳腺癌的血管生成和转移。
Tumor-educated macrophages facilitate tumor metastasis and angiogenesis. We discovered that GM-CSF blocked macrophages 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.