骨转移种子的选择是通过中介细胞信号在主要瘤流体中进行的
Xiang H-F Zhang1, Xin Jin1, Srinivas Malladi1
1Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Cell
|September 3, 2013
概括
乳腺瘤流体通过提供特定的生长因子来选择癌细胞进行骨转移. 这个过程启动了具有高Src活性的癌细胞扩散到骨髓.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 瘤微环境 瘤微环境
背景情况:
- 初级瘤中器官特异性转移性特征的起源尚不清楚.
- 瘤流层在塑造癌细胞向转移的进化中的作用是一个活跃的研究领域.
研究的目的:
- 为了研究乳腺瘤流体如何影响为骨转移准备的癌细胞的选择.
- 阐明癌症相关纤维细胞 (CAFs) 促进转移性特征发展的机制.
主要方法:
- 对三阴性 (TN) 乳腺瘤中的癌细胞种群的分析.
- 研究CAF衍生因子 (CXCL12和IGF1) 对癌细胞克隆的作用.
- 评估Src活性和PI3K-Akt通路激活在选定的癌细胞中.
主要成果:
- 乳腺瘤流体,特别是CAF,选择利用CXCL12和IGF1.1的癌细胞克隆.
- 这些因素的有限度对具有高Src活性的癌细胞具有选择性.
- 高Src活性增强PI3K-Akt通路的激活,为骨转移开启细胞.
结论:
- 主要瘤内的电流信号可以模仿来自遥远器官的线索,选择容易转移到该器官的癌细胞.
- 这种机制解释了器官特异性转移性特征的演变,并阐明了初级瘤在准备癌细胞远程传播中的作用.
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