从树突细胞转移到乳腺癌细胞的外体细胞调节了治疗耐药性途径
Mirjam C Boelens1, Tony J Wu1, Barzin Y Nabet1
1Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell
|November 24, 2014
概括
流体细胞与乳腺癌细胞通信,促进对化疗和辐射的耐药性. 这种交叉声涉及外体激活抗病毒信号和NOTCH3通路,导致耐治疗瘤生长.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肌肉癌细胞相互作用显著影响瘤进展和治疗结果.
- 了解治疗耐药性的机制对于开发有效的癌症治疗是至关重要的.
研究的目的:
- 阐明 stromal 沟通在调解乳腺癌对化疗和辐射耐药性的作用.
- 为了确定涉及介性疗法耐药性的特定信号通路.
主要方法:
- 研究了肌和乳腺癌细胞之间的对和对信号传递.
- 分析了外体转移及其RNA含量.
- 研究了RIG-I,STAT1和NOTCH3通道的激活.
- 利用初级人类和小鼠乳腺癌模型.
- 评估了与玛分泌酶抑制剂联合治疗的疗效.
主要成果:
- 流体细胞将含有非编码RNA和可移植元素的外体转移到乳腺癌细胞中.
- 外基因组衍生的RNA激活RIG-I和STAT1依赖的抗病毒信号.
- 干细胞激活乳腺癌细胞中的NOTCH3信号传递.
- STAT1增强了NOTCH3的转录反应,扩大了耐治疗瘤发起细胞.
- 抗病毒和NOTCH3通路对于乳腺癌中介性抗性至关重要.
结论:
- 流体细胞通过外部细胞与乳腺癌细胞进行复杂的交叉声调节,诱导抗病毒信号和NOTCH3激活.
- 这种相互作用促进了耐治疗乳腺癌亚种群的扩大.
- 针对这些途径的组合疗法,包括玛分泌酶抑制剂,可以废除斯特罗玛介导的耐药性.
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