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

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 our 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. We 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 a decrease in their spreading area. In addition, a decrease in the number of focal contacts 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, we developed a method which 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.