矩阵刚度协调细胞增殖和PD-L1表达通过YAP在肺腺癌中的肺腺癌
Yeonhee Park1, Dahye Lee2, Jeong Eun Lee2
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 34943, Republic of Korea.
矩阵刚度增加了YAP激活,导致肺腺癌细胞中更高的PD-L1和Ki-67表达. 这种YAP介导的途径将瘤微环境与细胞增殖和PD-L1水平联系起来.
科学领域:
- 在瘤学瘤学.
- 生物材料科学 生物材料科学
- 细胞生物学 细胞生物学
背景情况:
- 细胞外基质 (ECM) 在瘤进展中起着至关重要的作用,影响细胞行为并支持瘤生长.
- 增加的ECM刚度是固体瘤的标志,促进机械转导通路.
- 像YAP/TAZ,β-catenin和NF-κB这样的关键转录因子参与了ECM度介导的细胞反应.
研究的目的:
- 研究YAP在肺腺癌中作为矩阵刚性和PD-L1表达之间的调解者的作用.
- 为了确定由矩阵刚性的YAP激活是否影响PD-L1和细胞增殖标记.
主要方法:
- 肺腺癌细胞系 (PC9,HCC827) 在不同硬度的矩阵上培养 (体外2D).
- 在这些细胞中,YAP表达被操纵 (敲击和过度表达).
- 细胞增殖标记Ki-67和PD-L1表达在不同的硬度条件和YAP水平下进行了评估.
- 实验还在3D细胞培养模型中进行了实验,以获得生理学相关性.
主要成果:
- 在2D培养中,YAP,PD-L1和Ki-67表达水平随着矩阵刚度的增加而增加.
- 在YAP knockdown中,PD-L1和Ki-67的表达减少了,而YAP的过度表达则在刚性矩阵中增强了它们.
- 在3D培养模型中观察到类似的PD-L1和Ki-67的YAP依赖调节.
结论:
- 矩阵刚度通过肺腺癌中YAP激活来积极调节PD-L1表达.
- YAP充当关键的调解者,将瘤微环境的机械特性与PD-L1表达和细胞增殖联系起来.
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