慢性压力通过中性粒细胞介导的微环境变化增加转移
Xue-Yan He1, Yuan Gao1, David Ng1
1Cold Spring Harbor Laboratory, Cancer Center, Cold Spring Harbor, NY 11724, USA.
Cancer cell
|February 25, 2024
概括
慢性压力通过增加肺中的中性粒细胞外陷 (NETs) 来促进癌症转移. 准NET可以预防压力患者的癌症复发.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 压力生理学 压力生理学
背景情况:
- 慢性压力与更高的癌症转移和更差的生存率有关.
- 连接压力与癌症传播的潜在机制在很大程度上是未知的.
研究的目的:
- 为了研究慢性压力如何影响小鼠的肺转移.
- 确定压力诱导转移的细胞和分子媒介.
主要方法:
- 在慢性压力条件下的小鼠中评估肺转移.
- 分析了肺部的微环境,包括免疫细胞透和细胞外矩阵组件.
- 使用枯竭和遗传删除模型研究了中性粒细胞和中性粒细胞外细胞陷 (NETs) 的作用.
- 研究了DNase I对NET和转移的作用.
主要成果:
- 慢性压力增加了小鼠的肺转移2至4倍.
- 压力改变了肺部的微环境,其特点是纤维素蛋白积累,T细胞减少和中性粒细胞透增加.
- 中性粒细胞枯竭取消了压力诱导的转移.
- 慢性压力通过葡萄糖皮质体释放诱导了NET的形成,通过中性粒细胞特异性葡萄糖皮质体受体缺失来预防这种情况.
- 网的DNase I消化抑制了压力诱导的转移.
结论:
- 在慢性压力期间释放的葡萄皮质皮质激素促进了NET的形成.
- NETs建立了一个前转移性肺微环境.
- NETs代表了一种潜在的治疗点,用于预防患有慢性压力的癌症患者转移性复发.
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