界面压力调节乳腺癌与宿主界面的可塑性和耐药性
Bram G Soliman1,2, Peilin Tian1,2, Jiuyu Cui1,2
1School of Chemistry, University of New South Wales, Sydney, New South Wales, 2052, Australia.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|June 26, 2025
概括
乳腺癌细胞的物理限制通过促进干性增加药物耐药性. 准机械传导通路可能会克服这种被囚禁引起的固体压力,并提高治疗效率.
科学领域:
- 生物医学工程 生物医学工程
- 癌症生物学 癌症生物学
- 细胞力学 细胞力学
背景情况:
- 乳腺接口的细胞限制影响了乳腺癌的可塑性.
- 监禁压力与药物耐药性之间的联系在体外模型中缺乏,从而孤立了监禁的作用.
研究的目的:
- 开发一个模型系统来研究对乳腺癌细胞的限制诱导的固体压力.
- 为了研究身体限制,干性和乳腺癌中药物耐药性之间的关系.
主要方法:
- 利用按需点击打印,在酸盐水凝中创建受限的MCF-7乳腺癌球体.
- 药物耐药性 (多克索鲁比/塔莫西芬) 和干细胞标志物表达 (CD44+/CD133+) 在受限与未受限球体中进行比较.
- 评估了机制转导蛋白 (YAP,肌酸蛋白) 的药理抑制对药物耐药性的影响.
主要成果:
- 限制诱导了CD44+/CD133+干细胞在球形界面的出现.
- 与非受限对照相比,受限球体表现出多克索鲁比辛/塔莫西芬耐药性增加了两倍.
- 抑制YAP和髓素取消了干细胞表型并降低了耐药性.
结论:
- 建立了一个体外模型,用于研究乳腺癌的界面压力干性药物耐药性.
- 机械转导通路是限制诱导的耐药性的关键调解者.
- 针对这些途径提供了一个潜在的策略,以克服在乳腺癌治疗中强烈的压力驱动的耐药性.
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