PDF(Pubmed)
Abstract：
Brain metastases are the most lethal progression event, in part because the biological processes underpinning brain metastases are poorly understood. There is a paucity of realistic models of metastasis, as current in vivo murine models are slow to manifest metastasis. We set out to delineate metabolic and secretory modulators of brain metastases by utilizing two models consisting of in vitro microfluidic devices: 1) a blood brain niche (BBN) chip that recapitulates the blood-brain-barrier and niche; and 2) a migration chip that assesses cell migration. We report secretory cues provided by the brain niche that attract metastatic cancer cells to colonize the brain niche region. Astrocytic Dkk-1 is increased in response to brain-seeking breast cancer cells and stimulates cancer cell migration. Brain-metastatic cancer cells under Dkk-1 stimulation increase gene expression of FGF-13 and PLCB1. Further, extracellular Dkk-1 modulates cancer cell migration upon entering the brain niche.
摘要：
脑转移是最致命的进展事件，部分原因是对支撑脑转移的生物学过程知之甚少。缺乏现实的转移模型，因为目前体内小鼠模型缓慢显示转移。我们着手通过利用由体外微流体装置组成的两个模型来描绘脑转移的代谢和分泌调节剂:1)概括血脑屏障和生态位的血脑生态位(BBN)芯片;和2)评估细胞迁移的迁移芯片。我们报告了脑生态位提供的分泌线索，这些线索吸引转移性癌细胞定植于脑生态位区域。星形胶质细胞Dkk-1响应于脑寻求乳腺癌细胞而增加，并刺激癌细胞迁移。在Dkk-1刺激下的脑转移癌细胞增加FGF-13和PLCB1的基因表达。Further,细胞外Dkk-1在进入脑小生境后调节癌细胞迁移。
