シナプスの接近は,NMDAR信号が脳転移を促進することを可能にします
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
まとめ
乳がん細胞が脳に転移し ニューロンの経路を乗っ取ります N-メチル-D-アスパルテート受容体 (NMDARs) を活性化するためにニューロンと擬似シナプスを形成し,脳転移を引き起こします.
科学分野:
- 腫瘍学
- 神経科学
- 細胞生物学
背景:
- 癌が遠くの臓器に 転移することは がんによる死亡の主な原因です
- 乳腺から脳への転移 (B2BM) は乳がんの頻繁で壊滅的な合併症であり,特に攻撃的なサブタイプです.
- 乳がんが脳転移を好む 具体的なメカニズムは ほとんど解明されていません
研究 の 目的:
- 乳がんが脳を優位に支配する 分子機構を解明する
- 乳腺から脳への転移における 神経信号伝達経路の役割を調査する.
- 脳転移を予防または治療するための潜在的な治療標的を特定する.
主な方法:
- ヒトとマウスの乳がん細胞と脳組織の分析
- N-メチル-D-アスパルテート受容体 (NMDAR) のシグナル伝達経路の調査
- 癌細胞とニューロンの相互作用とシナプス形成をモデル化するコカルチャーシステム
主要な成果:
- 乳腺から脳への転移細胞は,N-メチル-D-アスパルテート受容体 (NMDARs) を活性化させ,これは脳植民に不可欠な神経信号伝達経路である.
- B2BM細胞はNMDARsを発現するが,オトクリン信号に十分なグルタミン酸を分泌しない.
- NMDARの活性化と脳転移を促す,グルタマタージックニューロンとの pseudo- tripartite シナプスを形成する.
- B2BMにおけるNMDARの活性化は,予後不良と関連しています.
結論:
- 乳がん細胞は NMDAR を通して神経のグルタミン酸信号を活用して脳に転移します
- 癌細胞とニューロンの間の 擬似シナプスの形成は 脳転移の鍵となるメカニズムです
- NMDAR経路またはこれらの擬似シナプスをターゲットにすることで,B2BMに対する新しい治療戦略を提供することができます.
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