在与恶性外围神经瘤细胞相关的巨细胞中引起TRAP1表达的前瘤功能
Francesca Scantamburlo1,2, Alessia Rubini1, Margherita Toffanin1,2
1Department of Biomedical Sciences, University of Padova, via Ugo Bassi 58/B, Padova, 35131, Italy.
Journal of experimental & clinical cancer research : CR
|August 28, 2025
概括
分子伴侣TRAP1重新编程巨细胞以促进恶性外围神经膜瘤 (MPNST) 的生长和血管生成. 这一TRAP1- Succinate- HIF-1α轴对于MPNST的瘤进展至关重要.
科学领域:
- 癌症学
- 癌症生物学
- 代谢途径
背景情况:
- 瘤微环境中的巨细胞表现出支持前瘤功能的代谢适应.
- 恶性外围神经瘤 (MPNST) 被巨细胞透,但它们在瘤生长中的作用尚不清楚.
- 分子伴侣TRAP1调节线粒体新陈代谢,并研究其在巨驱动的MPNST进展中的作用.
研究的目的:
- 在MPNST的背景下研究TRAP1在调节巨细胞表型和功能的作用.
- 确定TRAP1如何影响巨细胞与MPNST细胞和内皮细胞的相互作用.
主要方法:
- 在暴露于MPNST细胞调节介质的巨细胞中评估的表型变化,含有或不含TRAP1.
- 评估了这些修饰的巨细胞支持MPNST细胞生长,迁移和内皮细胞血管生成的能力.
主要成果:
- 在巨细胞 (原始和M2类) 中TRAP1表达对于获得亲新生体特征至关重要.
- 表达TRAP1的巨细胞促进MPNST的生长和迁移,并增强内皮细胞血管生成.
- 酸盐的积累和随后的HIF-1α激活介导了这些TRAP1依赖的前瘤效应.
结论:
- MPNST细胞释放诱导巨细胞瘤促进的表型变化的因素.
- 在巨细胞中TRAP1介导的代谢重编程对于维持这种支持瘤的交叉语音至关重要.
- 一个TRAP1-succinate-HIF-1α信号轴驱动着MPNST中的巨细胞的前瘤特征.
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