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首页> 外文期刊>Cancer Cell >A Positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis
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A Positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis

机译：间质样癌细胞与巨噬细胞之间的正反馈回路对于乳腺癌转移至关重要

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摘要

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 GM-CSF. 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.
机译：在肿瘤的侵袭性前沿，经历上皮-间质转化（EMT）和肿瘤相关巨噬细胞（TAM）的癌细胞非常接近，表明这两种细胞类型可能相互相互作用。我们显示，间充质样乳腺癌细胞通过GM-CSF激活巨噬细胞至TAM样表型。相反，来自TAM的CCL18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。抑制GM-CSF或CCL18打破了这种循环并减少了癌症转移。乳腺癌样品中高GM-CSF表达与更多的CCL18 +巨噬细胞，癌细胞EMT，转移增加和患者生存率降低相关。这些发现表明，GM-CSF和CCL18之间的正反馈回路在乳腺癌转移中很重要。

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