巨细胞从铁性死亡中拯救细胞
Ruth Hefetz1, Sapir Harush2, Lucy Ghantous1
1Goldyne Savad Institute of Gene Therapy, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Cell death & disease
|December 1, 2025
概括
巨细胞可以通过铁死来阻止癌细胞死亡,这是一种涉及铁和脂质过氧化的过程. 这种通过细胞间接触介导的保护作用,当巨细胞分化为M1型时,就会减少.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 癌症研究 癌症研究
背景情况:
- 铁,一种依赖于铁的细胞死亡形式,在器官损伤,退行性疾病和抗癌治疗中发挥作用.
- 虽然铁亡的细胞内机制已知,但影响细胞敏感性的细胞外因素仍然不清楚.
研究的目的:
- 研究巨细胞在癌细胞中调节铁亡的作用.
- 确定巨细胞影响铁亡的机制,并探索潜在的治疗应用.
主要方法:
- 不同类型的癌细胞与巨细胞共同培养.
- 使用GPX4抑制剂 (RSL3,ML162),GPX4沉默或Xc-系统抑制剂 (IKE) 诱导铁亡.
- 在铁细胞中评估细胞死亡,脂质过氧化和细胞表面标记物 (CD47,氨酸).
- 对巨细胞分化 (M1与M2) 和细胞间接触依赖性的评估.
主要成果:
- 巨细胞显著降低了癌细胞中的铁和脂质过氧化,无论铁的诱导因素是什么.
- 巨细胞的保护依赖于细胞间直接接触.
- 与M2相比,M1极化巨细胞表现出较低的保护能力.
- 铁细胞显示CD47的升高 ("不要吃我"信号) 和酸的降低 (PS",吃我"信号),促进巨细胞的相互作用.
- 巨细胞保护了胎盘子中的热囊细胞免受铁亡.
结论:
- 巨细胞具有未被识别的抗ferroptotic活性,作为细胞外部的保护机制.
- 癌细胞可能利用这种巨细胞介导的保护来逃避铁亡.
- 了解这种相互作用对于开发针对铁亡的新型癌症疗法至关重要.
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