Xu Jing, Galvanetto Nicola, Nie Jihua, Yang Yili, Torre Vincent
International School for Advanced Studies (SISSA), 34136 Trieste, Italy.
Joint Laboratory of Biophysics and Translational Medicine, Suzhou Institute of Systems Medicine (ISM)- International School for Advanced Studies (SISSA), Suzhou 215123, China.
Cancers (Basel). 2020 Jun 23;12(6):1667. doi: 10.3390/cancers12061667.
The failure of existing therapies in treating human glioblastoma (GBM) mostly is due to the ability of GBM to infiltrate into healthy regions of the brain; however, the relationship between cell motility and cell mechanics is not well understood. Here, we used atomic force microscopy (AFM), live-cell imaging, and biochemical tools to study the connection between motility and mechanics in human GBM cells. It was found thatRac1 inactivation by genomic silencing and inhibition with EHT 1864 reduced cell motility, inhibited cell ruffles, and disrupted the dynamics of cytoskeleton organization and cell adhesion. These changes were correlated with abnormal localization of myosin IIa and a rapid suppression of the phosphorylation of Erk1/2. At the same time, AFM measurements of the GBM cells revealed a significant increase in cell elasticity and viscosity following Rac1 inhibition. These results indicate that mechanical properties profoundly affect cell motility and may play an important role in the infiltration of GBM. It is conceivable that the mechanical characters might be used as markers for further surgical and therapeutical interventions.
现有疗法在治疗人类胶质母细胞瘤（GBM）时大多失败，这主要是由于GBM能够浸润到大脑的健康区域；然而，细胞运动性与细胞力学之间的关系尚未得到充分理解。在此，我们使用原子力显微镜（AFM）、活细胞成像和生化工具来研究人类GBM细胞中运动性与力学之间的联系。研究发现，通过基因沉默和用EHT 1864抑制使Rac1失活，可降低细胞运动性，抑制细胞皱褶，并破坏细胞骨架组织和细胞黏附的动力学。这些变化与肌球蛋白IIa的异常定位以及Erk1/2磷酸化的快速抑制相关。同时，对GBM细胞的AFM测量显示，Rac1抑制后细胞弹性和黏度显著增加。这些结果表明，力学性质深刻影响细胞运动性，可能在GBM浸润中起重要作用。可以想象，力学特征可能用作进一步手术和治疗干预的标志物。
