单细胞测序揭示了感觉神经元介导的CGRP信号作为肉瘤进展的驱动因素
Sowmya Ramesh1, Qizhi Qin1, Zhao Li1
1Department of Pathology, Johns Hopkins University, Baltimore, MD 21205.
概括
在骨髓瘤 (OS) 中准神经生长可以减少瘤的进展和转移. 抑制TrkA表达的感觉神经元和素基因相关 (CGRP) 信号传递显著改善骨癌模型中的生存率.
科学领域:
- 在瘤学瘤学.
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 骨头疼痛是骨髓瘤 (OS) 的常见症状,通常由感觉神经元介导.
- 除了疼痛之外,与瘤相关的感觉神经元在骨癌中的作用尚不清楚.
研究的目的:
- 研究神经神经元在骨髓瘤进展中的感觉神经元的神经调节功能.
- 探索针对OS神经内生长的治疗策略.
主要方法:
- 在小鼠中采用化学遗传方法,使用TrkA敲进等位基因来抑制OS期间的感觉神经功能.
- 在小鼠和人类OS样本上采用单细胞转录组学和多细胞组学分析.
- 重新使用FDA批准的布皮瓦卡因脂质体和Rimegepant来抑制神经内生和CGRP信号传递.
主要成果:
- 抑制TrkA显著降低了与OS相关的感官内置,血管化,瘤生长和转移,同时延长了生存时间.
- 化改变了瘤细胞和微环境的表型,减少了素基因相关 (CGRP) 和血管内皮生长因子 (VEGF) 信号.
- 布皮瓦卡因脂质体和CGRP抑制策略都显著降低了肉瘤的生长,血管性和过敏症.
结论:
- 表达TrkA的外围神经元积极调节骨髓瘤进展的关键方面.
- 抑制感觉神经信号传递,特别是CGRP,破坏了肉瘤微环境,减少瘤生长并改善生存率.
- 针对OS的病理性内化提供了潜在的辅助疗法,以提高临床结果和生存率.
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