突触接近使NMDAR信号能够促进大脑转移
Qiqun Zeng1,2, Iacovos P Michael1,2, Peng Zhang3
1Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Nature
|September 20, 2019
概括
乳腺癌细胞转移到大脑, 劫持神经元通路. 它们与神经元形成伪突触以激活N-甲基-D-阿斯巴酸受体 (NMDARs),从而驱动大脑转移.
科学领域:
- 癌症学
- 神经科学
- 细胞生物学
背景情况:
- 癌症转移到远处的器官是癌症相关死亡的主要原因.
- 乳腺转移到大脑 (B2BM) 是乳腺癌的常见并发症,特别是在侵袭性亚型中.
- 导致乳腺癌偏向大脑转移的具体机制至今尚不清楚.
研究的目的:
- 揭示乳腺癌在大脑中占据优势的分子机制.
- 研究神经元信号通路在乳腺转移到大脑中的作用.
- 确定预防或治疗大脑转移的潜在治疗点.
主要方法:
- 分析人类和小鼠的乳腺癌细胞和脑组织.
- 对N-甲基-D-酸盐受体 (NMDAR) 信号通路的研究.
- 共同培养系统以建模癌细胞与神经元的相互作用和突触形成.
主要成果:
- 乳腺转移到大脑的细胞激活N-甲基-D-酸盐受体 (NMDARs),这是神经元信号通路,对大脑定居至关重要.
- B2BM细胞表达NMDARs,但不够分泌谷氨酸进行自身分泌信号.
- 癌细胞与谷氨酸性神经元形成伪三方突触,使NMDAR激活并驱动大脑转移.
- 在B2BM中NMDAR激活与预后不佳有关.
结论:
- 乳腺癌细胞通过NMDAR利用神经元的谷氨酸信号向大脑转移.
- 癌细胞与神经元之间的伪突触形成是大脑转移的关键机制.
- 针对NMDAR途径或这些伪突触可能为B2BM提供新的治疗策略.
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