Microglia Promote Colonization of Brain Tissue by Breast Cancer Cells in a Wnt-Dependent Way
Microglia Promote Colonization of Brain Tissue by Breast Cancer Cells in a Wnt-Dependent Way
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DOI：
10.1002/glia.21022
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发表时间：
2010-09-01
期刊：
影响因子：
6.2
通讯作者：
Binder, Claudia
中科院分区：
文献类型：
--
作者：
Pukrop, Tobias;Dehghani, Faramarz;Binder, Claudia
尽管越来越多的证据表明血液来源的巨噬细胞支持肿瘤进展，但仍不清楚特化的常驻巨噬细胞（如脑小胶质细胞）是否也在转移形成中发挥重要作用。在这里，我们表明，小胶质细胞增强乳腺癌细胞对脑组织的侵袭和定植，既作为主动转运蛋白，又作为导轨。这通过小胶质细胞的失活以及Wnt抑制剂Dickkopf-2来拮抗。前侵袭性小胶质细胞表现出改变的形态，但既不上调M2样细胞因子，也不差异基因表达。细菌脂多糖将受肿瘤训练的小胶质细胞转变为经典的M1表型，降低其促侵袭功能，并揭示炎症和Wnt信号传导是最强烈的调节途径。人脑转移瘤的组织学发现强调了这些结果的意义。总之，小胶质细胞是成功的上皮癌细胞的大脑的殖民地的关键，这表明作为一个有前途的抗转移策略的抑制proinvasive小胶质细胞。(C)2010 Wiley-Liss，Inc.
Although there is increasing evidence that blood-derived macrophages support tumor progression, it is still unclear whether specialized resident macrophages, such as brain microglia, also play a prominent role in metastasis formation. Here, we show that microglia enhance invasion and colonization of brain tissue by breast cancer cells, serving both as active transporters and guiding rails. This is antagonized by inactivation of microglia as well as by the Wnt inhibitor Dickkopf-2. Proinvasive microglia demonstrate altered morphology, but neither upregulation of M2-like cytokines nor differential gene expression. Bacterial lipopolysacharide shifts tumor-educated microglia into a classical M1 phenotype, reduces their proinvasive function, and unmasks inflammatory and Wnt signaling as the most strongly regulated pathways. Histological findings in human brain metastases underline the significance of these results. In conclusion, microglia are critical for the successful colonization of the brain by epithelial cancer cells, suggesting inhibition of proinvasive microglia as a promising antimetastatic strategy. (C) 2010 Wiley-Liss, Inc.