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淋巴细胞保护转移的黑色素瘤细胞免受铁

Jessalyn M Ubellacker¹, Alpaslan Tasdogan¹, Vijayashree Ramesh¹

¹Children's Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

|August 21, 2020

概括

淋巴细胞中的黑色素瘤细胞经历的氧化压力较小,并且比血液中的细胞形成更多的转移. 淋巴环境保护癌细胞免受铁,增强它们的生存和扩散.

科学领域:

癌症学
细胞生物学
癌症转移

背景情况:

黑色素瘤在系统性扩散之前经常通过淋巴细胞转移,但潜在的机制尚不清楚.
了解淋巴细胞与血液循环系统中的黑色素瘤细胞的差异行为对于开发向疗法至关重要.

研究的目的:

研究为什么淋巴系统中的黑色素瘤细胞与血液中的细胞具有不同的转移潜力.
通过不同的途径阐明氧化应激和铁死在黑色素瘤转移中的作用.

主要方法:

从患者和小鼠模型中抽取瘤淋巴和血液中的黑色素瘤细胞的比较分析
评估来自不同转移环境的黑色素瘤细胞的依赖性 (GPX4) 和耐药性.
使用铁抑制剂和油酸治疗的体内实验.

主要成果:

淋巴细胞中的黑色素瘤细胞比血液中的细胞减少了氧化应激和转移能力.
通过血液而不是淋巴转移的细胞依赖GPX4生存.
淋巴液含有较高的谷和油酸,较少的自由铁,有助于降低铁.

结论:

淋巴环境赋予黑色素瘤细胞的耐药性,提高了它们的存活率和转移潜力.
淋巴中的油酸通过Acsl3保护黑色素瘤细胞免受铁亡并促进瘤形成.
适应淋巴系统的黑色素瘤细胞对铁变更耐药,并形成更多的血液转移.

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