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肺转移不需要表皮细胞转移到介质细胞,但有助于化学抵抗
Kari R Fischer1,2,3,4, Anna Durrans1,2,3, Sharrell Lee1,2,3
1Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Nature
|November 13, 2015
概括
在化疗后复发的乳腺癌转移过程中,瘤细胞经历了上皮转移至介质细胞 (EMT) 的转变至关重要. 针对EMT可能会提高传统化疗的疗效.
科学领域:
- 癌症学
- 癌症生物学
- 分子生物学
背景情况:
- 由于体内监测存在挑战,因此在癌症转移中表皮细胞转移到介质细胞转移 (EMT) 的作用受到争议.
- 了解EMT动态对于开发有效的癌症疗法至关重要.
研究的目的:
- 建立一个血统追踪系统来监测体内EMT.
- 研究EMT对乳腺癌转移和化学抵抗的作用.
主要方法:
- 在小鼠中开发一种中细胞特异性的光标记开关系统.
- 使用自发的乳腺到肺转移模型.
- 使用微RNA (miR-200) 操纵来抑制EMT.
主要成果:
- 一小部分原发性瘤细胞接受EMT,而转移主要是上皮细胞.
- 抑制EMT没有影响初始肺转移的发展.
- 对环胺的EMT细胞的存活率和化疗抵抗性增加,而miR-200可以逆转这种情况.
- 在化疗后,EMT细胞对复发的转移有显著的贡献.
结论:
- 在最初的转移中,EMT不是必不可少的,但对于复发和化疗抵抗来说至关重要.
- 与化疗相结合的EMT向策略在乳腺癌治疗中具有前景.
- 在EMT细胞中,miR-200在消除化学抵抗方面发挥作用.
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