瘤内部的氧化热点为癌细胞扩散提供了一个利基
Yoshifumi Ueda1, Shigeki Kiyonaka2,3,4, Laura M Selfors5
1Department of Synthetic Chemistry and Biological Chemistry, Kyoto University, Kyoto, Japan.
Nature cell biology
|February 21, 2025
概括
研究人员开发了一种新的探针来追踪瘤中的氧化应激. 这揭示了由中性粒细胞驱动的过氧化 (H2O2) 热点,促进癌细胞迁移和转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 瘤内部异质性包括遗传,表型和微环境因素.
- 虽然遗传和表型变异性已被理解,但微环境异质性仍然具有挑战性.
- 氧化应激,癌症的标志,显著影响瘤微环境.
研究的目的:
- 开发一种用于可视化和描述瘤内微环境氧化应激的工具.
- 研究细胞外过氧化 (H2O2) 在瘤细胞行为和转移中的作用.
- 阐明癌细胞适应氧化应激的机制.
主要方法:
- 开发T-AP1,一种针对瘤的探针,用于追踪细胞外H2O2.2.
- 在瘤中可视化和描述富含H2O2的微环境 (热点).
- 对瘤细胞对H2O2的反应的分析,包括上皮-介质细胞过渡和迁移通路 (p38-MYC轴).
主要成果:
- T-AP1确定了H2O2热点,主要由中性粒细胞建立,在活跃芽的瘤区域内.
- 暴露于H2O2的瘤细胞经历了部分上皮层-介质细胞过渡,并通过p38-MYC激活从热点迁移.
- 这种迁移性逃生机制在大多数癌症中被观察到,但在NRF2过度激活的瘤中没有,这些瘤显示出增强的抗氧化防御能力.
结论:
- H2O2热点作为一个利基,促进癌细胞扩散和转移的启动.
- T-AP1是一个有价值的工具,用于识别这些关键的微环境.
- 癌细胞拥有内在的应激防御程序,如p38-MYC轴,以逃避氧化应激并促进入侵.
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