骨质细胞衍生的酸触发休眠的肺腺癌细胞激活
Xingyu Liu1, Rong Qiu1, Pengcheng Gui1
1Department of Laboratory Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
iScience
|April 24, 2025
概括
来自骨质细胞的酸 (AA) 会在骨中重新激活休眠的肺腺癌 (LUAD) 细胞. 这种通过CD36的AA转移激活了PPARγ-ANGPTL4通路,为LUAD骨转移提供了潜在的生物标志物.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移 癌症转移
背景情况:
- 骨中的休眠肺腺癌 (LUAD) 细胞可以重新激活并导致转移性疾病.
- 骨质细胞相互作用与这些休眠瘤细胞的重新激活有关.
研究的目的:
- 为了识别从骨质细胞转移到休眠的LUAD细胞的启动分子.
- 阐明骨微环境中LUAD细胞活性化的分子机制.
- 探索LUAD骨转移的潜在生物标志物和治疗点.
主要方法:
- 利用3D休眠模型和小鼠骨转移模型.
- 研究了阿拉基酸 (AA) 的作用及其通过CD36.6的吸收.
- 分析了PPARγ-ANGPTL4通路的激活.
- 在有骨转移和没有骨转移的患者中测量了AA和ANGPTL4的血清水平.
主要成果:
- 阿拉基酸 (AA) 被确定为从骨质细胞转移到休眠的LUAD细胞的启动分子.
- 休眠的LUAD细胞通过CD36吸收AA,激活PPARγ-ANGPTL4通路,从而导致瘤细胞的激活.
- 对AA的激活效应观察到剂量反应关系,抑制AA代谢阻止了重新激活.
- 在临床骨转移的患者中,AA和ANGPTL4的血清水平显著升高.
结论:
- 骨质细胞通过CD36-PPARγ-ANGPTL4轴传递AA,以激活休眠的LUAD细胞.
- AA和ANGPTL4显示出作为预测和监测LUAD骨转移的有价值生物标志物的潜力.
- 准AA途径为治疗LUAD骨转移提供了潜在的临床应用.
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