通过原重塑的CAF驱动机械传导加速瘤细胞周期的进展
Yating Xiao1,2, Yingying Jiang1,2, Ting Bao3
1Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164, China.
Gels (Basel, Switzerland)
|August 28, 2025
概括
与癌症相关的纤维细胞 (CAF) 会使原凝变硬,通过机械应激促进乳腺癌细胞的增殖. 针对这些CAF介导的变化为癌症治疗提供了一种新的治疗策略.
科学领域:
- 生物医学工程
- 癌症生物学
- 机械生物学
背景情况:
- 癌症相关纤维细胞 (CAF) 重塑瘤微环境,影响癌症的进展.
- 传统的水凝模型未能捕捉到对于理解局部硬度对细胞行为的影响至关重要的空间异质性.
研究的目的:
- 开发一种新的微组织平台,研究与癌症相关的纤维细胞诱导的原体水凝改造如何影响乳腺癌细胞的增殖.
- 阐明局部度梯度调节癌细胞周期进展的生物机械机制和信号通路.
主要方法:
- 开发一个可编程微链的原微组织平台,用于机械量化.
- 整合FUCCI细胞循环生物传感器和分子扰动来监测细胞循环和信号.
- 实时测量凝密度,硬度变化和孔径缩小.
主要成果:
- CAF收缩显著增加了水凝的硬度 (350至775帕),并减少了孔径 (5.0至1. 9微米).
- 通过原 - 整合素 - 动肌素信号传递激活了YAP/TAZ核转移,导致癌细胞增殖2. 4倍.
- 药理上抑制YAP,actomyosin或原可以逆转这些效应,在CYR61中断后观察到部分恢复.
结论:
- 由CAF重塑的原体水凝作为瘤生长的关键生物机械调节剂.
- 针对CAF介导的机制传导途径是一个有前途的抗癌治疗策略.
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