A Positive Feedback Loop between Mesenchymal-like Cancer Cells and Macrophages Is Essential to Breast Cancer Metastasis
A Positive Feedback Loop between Mesenchymal-like Cancer Cells and Macrophages Is Essential to Breast Cancer Metastasis
复制标题
间充质样癌细胞和巨噬细胞之间的正反馈回路对于乳腺癌转移至关重要。
DOI：
10.1016/j.ccr.2014.03.021
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发表时间：
2014-05-12
期刊：
影响因子：
50.3
通讯作者：
Song, Erwei
中科院分区：
文献类型：
--
作者：
Su, Shicheng;Liu, Qiang;Song, Erwei
在肿瘤的侵袭性前沿，经历上皮-间质转化（EMT）的癌细胞和肿瘤相关巨噬细胞（TAM）的紧密邻近表明这两种细胞类型可能相互作用。我们发现，间充质样乳腺癌细胞激活巨噬细胞的TAM样表型的GMCSF。反过来，来自TAM的CCL 18在共培养系统和人源化小鼠中诱导癌细胞EMT，形成正反馈回路。GM-CSF或CCL 18的抑制打破了这一循环并减少了癌症转移。乳腺癌样本中GM-CSF的高表达与更多的CCL 18（+）巨噬细胞、癌细胞EMT、增强的转移和降低的患者存活率相关。这些发现表明GM-CSF和CCL 18之间的正反馈回路在乳腺癌转移中是重要的。
The close vicinity of cancer cells undergoing epithelial-mesenchymal transition (EMT) and tumor-associated macrophages (TAMs) at the invasive front of tumors suggests that these two cell type may mutually interact. We show that mesenchymal-like breast cancer cells activate macrophages to a TAM-like phenotype by GMCSF. Reciprocally, CCL18 from TAMs induces cancer cell EMT, forming a positive feedback loop, in coculture systems and humanized mice. Inhibition of GM-CSF or CCL18 breaks this loop and reduces cancer metastasis. High GM-CSF expression in breast cancer samples is associated with more CCL18(+) macrophages, cancer cell EMT, enhanced metastasis, and reduced patient survival. These findings suggest that a positive feedback loop between GM-CSF and CCL18 is important in breast cancer metastasis.