Department of Hematology/Oncology, University of Göttingen, Göttingen, Germany.
Glia. 2010 Sep;58(12):1477-89. doi: 10.1002/glia.21022.
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.
尽管越来越多的证据表明血液来源的巨噬细胞支持肿瘤的进展，但目前尚不清楚专门的驻留巨噬细胞（如脑小胶质细胞）是否也在转移形成中发挥突出作用。在这里，我们发现小胶质细胞增强了乳腺癌细胞对脑组织的侵袭和定植，既作为活跃的转运体又作为导轨。小胶质细胞失活以及 Wnt 抑制剂 Dickkopf-2 拮抗了这种作用。促侵袭性小胶质细胞表现出改变的形态，但既没有上调 M2 样细胞因子，也没有差异基因表达。细菌脂多糖将肿瘤诱导的小胶质细胞转变为经典的 M1 表型，降低了它们的促侵袭功能，并揭示了炎症和 Wnt 信号作为最强调节的途径。人类脑转移中的组织学发现强调了这些结果的重要性。总之，小胶质细胞对于上皮癌细胞成功定植大脑至关重要，提示抑制促侵袭性小胶质细胞是一种有前途的抗转移策略。
