在体内相互作用查显示肝脏衍生的转移约束
Costanza Borrelli1, Morgan Roberts1, Davide Eletto1
1Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Nature
|July 24, 2024
概括
研究人员发现肝脏蛋白质B2对于癌细胞来说至关重要. 阻止这种相互作用可以防止肝脏转移,为预防二次瘤提供新的治疗策略.
科学领域:
- 癌症生物学
- 转移研究
- 肝病学
背景情况:
- 只有很小一部分的瘤细胞成功形成明显的转移,这表明存在重要的环境约束.
- 控制转移播种和肝脏殖民的宿主因素在很大程度上是未知的.
- 了解宿主与瘤之间的相互作用对于开发有效的抗转移疗法至关重要.
研究的目的:
- 系统地研究肝脏转移的宿主因素,特别是肝细胞相互作用.
- 在结直肠癌,胰腺癌和黑色素瘤中识别新型宿主衍生的肝脏殖民调节剂.
- 阐明肝转移背后的分子机制,并探索潜在的治疗点.
主要方法:
- 开发一种 in vivo CRISPR 激活屏幕,该屏幕结合了转子子技术和光位标签.
- 在同基因小鼠模型中对肝细胞和转移细胞之间的相互作用进行系统研究.
- 在瘤细胞适应过程中涉及plexin B2,semaphorins和KLF4的分子途径的剖析.
主要成果:
- 在结直肠癌,胰腺癌和黑色素瘤中,Plexin B2被确定为肝脏殖民的关键宿主衍生调节剂.
- 在瘤细胞上,Plexin B2 与IV类半素相互作用,对KLF4进行上调,并促进殖民所需的上皮特征.
- 在临床前模型中,阻断plexin B2-semaphorin轴显著消除了肝脏转移殖民.
结论:
- 肝膜信号对于扩散的瘤细胞的初始播种和适应至关重要.
- 在结直肠癌 (CRC) 转移到肝脏时,需要由plexin B2-semaphorin-KLF4轴驱动的上皮化.
- 向B2-semaphorin轴为预防肝转移提供了一个有前途的治疗策略.
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