In vivo, migrating cells often encounter microenvironments that impose spatial constraints, leading to cell and nuclear deformation. As confinement-induced DNA damage has been linked to the accumulation of reactive oxygen species (ROS), we sought to investigate the impact of oxidative stress on cell behavior within confined spaces. Using microchannel devices that enable control of the degree and duration of cell confinement, we demonstrate that confined migration increases ROS levels in both HT-1080 fibrosarcoma cells and human dermal fibroblasts. Treatment with the antioxidant N-Acetyl-L-cysteine (NAC) counteracts confinement-induced ROS accumulation, suppressing p53 activation and supporting cell survival in both cell lines. This intervention preferentially reduces dorsal perinuclear actin fibers in confined cancer cells. Loss of these fibers is associated with reduced nuclear rupture frequency and increased confined migration speed. Collectively, this work provides insights into the differential effects of ROS on cancerous and non-cancerous cells and suggests that antioxidants may support tumor progression.

中文翻译：

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限制诱导的活性氧积累对高度运动的癌细胞和非癌细胞的不同影响


在体内，迁移细胞经常会遇到施加空间限制的微环境，导致细胞和细胞核变形。由于限制诱导的 DNA 损伤与活性氧 （ROS） 的积累有关，我们试图研究氧化应激对受限空间内细胞行为的影响。使用能够控制细胞限制程度和持续时间的微通道设备，我们证明限制迁移会增加 HT-1080 纤维肉瘤细胞和人真皮成纤维细胞中的 ROS 水平。用抗氧化剂 N-乙酰基-L-半胱氨酸 （NAC） 处理可抵消限制诱导的 ROS 积累，抑制 p53 活化并支持两种细胞系的细胞存活。这种干预优先减少局限癌细胞中的背侧核周肌动蛋白纤维。这些纤维的丢失与核破裂频率降低和受限迁移速度增加有关。总的来说，这项工作提供了对 ROS 对癌细胞和非癌细胞的不同影响的见解，并表明抗氧化剂可能支持肿瘤进展。