Endoplasmic Reticulum Stress Inducer Dithiothreitol Affects the Morphology and Motility of Cultured Human Dermal Fibroblasts and Fibrosarcoma HT1080 Cell Line

Pub Date : 2024-01-11 DOI:10.1134/s1062360423050065
E. P. Turishcheva, G. A. Ashniev, M. S. Vildanova, E. A. Smirnova
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Abstract

Some inducers of endoplasmic reticulum (ER) stress can affect the motility of normal and tumor cells. However, it is unknown what mechanisms mediate this effect and whether it is a consequence of ER stress. The aim of the present work was to study the effect of the ER stress inducer dithiothreitol (DTT) on morphological features reflecting the locomotor properties of cells as well as directly on the migratory properties of cultured human dermal fibroblasts and fibrosarcoma HT1080 cells. The authors have shown that DTT causes disruption of the organization of actin cytoskeleton in both types of cells, which is accompanied by a change in the cell surface and shape of cells, as well as in a decrease in their spreading area. In addition, a decrease in the number of focal adhesions was observed in dermal fibroblasts. DTT also reduced the motility of dermal fibroblasts and fibrosarcoma cells. To analyze cell motility and determine the moment of its change, the authors developed a method that showed that the change in the migratory properties of fibrosarcoma cells cultured with DTT began earlier than in dermal fibroblasts. Thus, activation of ER stress by DTT is accompanied by a change in the organization of the actin cytoskeleton and motility in normal and tumor human cells. Consequently, ER stress triggered by various inducers with different mechanisms of action affects the motility of normal and tumor cells, which must be taken into account when developing antitumor drugs that cause cell death through activation of ER stress.

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内质网应激诱导剂二硫苏糖醇影响培养的人真皮成纤维细胞和纤维肉瘤 HT1080 细胞系的形态和运动性
摘要内质网(ER)应激的某些诱导剂可影响正常细胞和肿瘤细胞的运动。然而,目前还不清楚是什么机制介导了这种效应,以及它是否是ER应激的结果。本研究的目的是研究ER应激诱导剂二硫苏糖醇(DTT)对反映细胞运动特性的形态特征的影响,以及直接对培养的人真皮成纤维细胞和纤维肉瘤HT1080细胞迁移特性的影响。作者的研究表明,DTT 会破坏这两种细胞的肌动蛋白细胞骨架组织,并伴随着细胞表面和细胞形状的变化,以及细胞扩散面积的减少。此外,在真皮成纤维细胞中还观察到局灶粘连数量的减少。DTT 还会降低真皮成纤维细胞和纤维肉瘤细胞的运动能力。为了分析细胞的运动性并确定其发生变化的时间,作者开发了一种方法,该方法显示,用 DTT 培养的纤维肉瘤细胞的迁移特性的变化开始得比真皮成纤维细胞早。因此,在正常细胞和肿瘤细胞中,DTT 对 ER 应激的激活伴随着肌动蛋白细胞骨架组织和运动性的改变。因此,由不同作用机制的诱导剂引发的ER应激会影响正常细胞和肿瘤细胞的运动,在开发通过激活ER应激导致细胞死亡的抗肿瘤药物时必须考虑到这一点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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