Department of Chemical and Biological Engineering, College of Engineering, The University of Alabama, Tuscaloosa, Alabama, USA.
Cells Tissues Organs. 2022;211(3):282-293. doi: 10.1159/000516574. Epub 2021 Jun 2.
Most cancer deaths are caused by secondary metastasized tumors. The cells that spread these tumors are known as circulating tumor cells (CTCs). They exist in a dynamic environment, including exposure to fluid shear stress (FSS) that makes them susceptible to reactive oxygen species (ROS) generation. There are questions about the similarities of CTCs to cancer stem cells (CSCs) and whether the stem cell-like characteristics of CTCs allow them to proliferate and spread despite the biophysical obstacles during the metastatic process. One of those qualities is the ability to undergo the epithelial-to-mesenchymal transition (EMT). Here, MDA-MB-231 and MCF7 were modeled as CTCs by prolonged exposure to FSS using a spinner flask. They were tested for ROS generation, CSC, EMT, and Hippo pathway gene and protein markers using qRT-PCR and flow cytometry. MDA-MB-231 did not show significant changes in CSC markers, but did show significant changes in ROS, EMT, and Hippo markers (p < 0.05). Similarly, MCF7 showed significant changes in ROS and EMT markers (p < 0.05). Furthermore, both cell lines demonstrated the reverse mesenchymal-to-epithelial transition signature when allowed to recover after FSS. These results suggest that the degree of their stemness or aggressiveness affects their responses to externally applied biophysical forces and demonstrates a potential link between mechanotransduction, the Hippo pathway, and the induction of EMT in breast cancer cells.
大多数癌症死亡是由继发性转移肿瘤引起的。这些肿瘤扩散的细胞被称为循环肿瘤细胞（CTC）。它们存在于动态环境中，包括暴露于流体切应力（FSS），这使它们容易产生活性氧物种（ROS）。目前存在一些问题，例如 CTC 与癌症干细胞（CSC）的相似性，以及 CTC 是否具有类似干细胞的特征，使其能够在转移过程中尽管存在生物物理障碍仍能增殖和扩散。其中一个特性是能够经历上皮-间充质转化（EMT）。在这里，通过在旋转瓶中长时间暴露于 FSS，将 MDA-MB-231 和 MCF7 模拟为 CTC。使用 qRT-PCR 和流式细胞术测试了它们的 ROS 生成、CSC、EMT 和 Hippo 途径基因和蛋白标志物。MDA-MB-231 的 CSC 标志物没有明显变化，但 ROS、EMT 和 Hippo 标志物有明显变化（p < 0.05）。类似地，MCF7 的 ROS 和 EMT 标志物也有明显变化（p < 0.05）。此外，当允许两条细胞系在 FSS 后恢复时，它们都表现出反向的间充质-上皮转化特征。这些结果表明，它们的干性或侵袭性程度会影响它们对外部施加的生物物理力的反应，并表明机械转导、Hippo 途径和乳腺癌细胞 EMT 诱导之间存在潜在联系。
