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内皮细胞的FAK向使瘤对破坏DNA的治疗敏感

Bernardo Tavora¹, Louise E Reynolds², Silvia Batista²

¹Adhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute, CR-UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.

|August 1, 2014

概括

在内皮细胞中准焦粘附激酶 (FAK) 增强了瘤细胞对化疗的敏感性. 这种新的机制抑制瘤生长,在人类淋巴瘤缓解中显示出临床相关性.

科学领域:

分子生物学分子生物学
癌症研究癌症研究
内皮细胞生物学内皮细胞生物学

背景情况:

化学抵抗仍然是癌症治疗中的一个重大障碍.
以前的研究主要集中在瘤细胞上,忽视了其他细胞贡献.
内皮细胞在调节治疗疗效方面发挥着至关重要的,但尚未研究的作用.

研究的目的:

确定由内皮细胞影响癌症化学抵抗的新型分子机制.
研究内皮细胞中焦粘附激酶 (FAK) 在调节瘤细胞对破坏DNA的疗法的敏感性方面的作用.
探索向内皮细胞的治疗潜力,以改善癌症治疗结果.

主要方法:

在小鼠模型中的内皮细胞中FAK的遗传删除.
使用破坏DNA的疗法 (多克索鲁比,放射治疗).
瘤生长,亡,扩散和NF-κB激活的评估.
在体外和体内活体内对内皮细胞中细胞因子生产的分析.
在人类淋巴瘤患者中,FAK表达与临床缓解的相关性.

主要成果:

准内皮细胞中的FAK使瘤细胞对破坏DNA的药物敏感,抑制小鼠的瘤生长.
内皮FAK删除并没有损害血管功能,但增强了瘤细胞亡和减少了增殖.
内皮FAK对于DNA损伤诱导的NF-κB激活和随后的细胞因子产生至关重要,这些细胞因子在FAK丢失时会减少.

结论:

内皮细胞FAK是瘤化学抵抗的关键调节者.
向内皮细胞的FAK是一种新的策略,可以提高DNA损伤癌症疗法的疗效.
瘤血管中的低FAK表达与人类淋巴瘤的完全缓解相关,支持临床相关性.

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