BMP4 Inhibits Breast Cancer Metastasis by Blocking Myeloid-Derived Suppressor Cell Activity
BMP4 Inhibits Breast Cancer Metastasis by Blocking Myeloid-Derived Suppressor Cell Activity
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DOI：
10.1158/0008-5472.can-13-3171
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发表时间：
2014-09-15
期刊：
影响因子：
11.2
通讯作者：
Anderson, Robin L.
中科院分区：
文献类型：
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作者：
Cao, Yuan;Slaney, Clare Y.;Anderson, Robin L.
TGF - β生长因子家族成员BMP4是乳腺癌转移的有效抑制因子。在小鼠中，高度转移性乳腺肿瘤的发展与髓源性抑制细胞（MDSC）的积累有关，其数量因外源性BMP4表达而减少。MDSCs在幼稚小鼠中检测不到，但可以通过粒细胞集落刺激因子（G-CSF/Csf3）或肿瘤分泌G-CSF诱导。肿瘤诱导的和g - csf诱导的MDSCs都能有效抑制t细胞的活化和增殖，导致转移增强。BMP4通过抑制NF-kappa B （Nfkb1）活性在人和小鼠肿瘤细胞系中降低G-CSF的表达和分泌。由于MDSCs与乳腺癌患者的不良预后相关，基于BMP4信号激活的治疗可能为乳腺癌提供一种新的治疗策略。(c) 2014年aacr。
The TGF beta growth factor family member BMP4 is a potent suppressor of breast cancer metastasis. In the mouse, the development of highly metastatic mammary tumors is associated with an accumulation of myeloid-derived suppressor cells (MDSC), the numbers of which are reduced by exogenous BMP4 expression. MDSCs are undetectable in naive mice but can be induced by treatment with granulocyte colony-stimulating factor (G-CSF/Csf3) or by secretion of G-CSF from the tumor. Both tumor-induced and G-CSF-induced MDSCs effectively suppress T-cell activation and proliferation, leading to metastatic enhancement. BMP4 reduces the expression and secretion of G-CSF by inhibiting NF-kappa B (Nfkb1) activity in human and mouse tumor lines. Because MDSCs correlate with poor prognosis in patients with breast cancer, therapies based on activation of BMP4 signaling may offer a novel treatment strategy for breast cancer. (C) 2014 AACR.