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患者来源的结肠直肠癌细胞的直流电场刺激

Direct-Current Electrical Field Stimulation of Patient-Derived Colorectal Cancer Cells.

作者信息

Lange Falko, Porath Katrin, Sellmann Tina, Einsle Anne, Jaster Robert, Linnebacher Michael, Köhling Rüdiger, Kirschstein Timo

机构信息

Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany.

Division of Gastroenterology and Endocrinology, Department of Medicine II, Rostock University Medical Center, 18057 Rostock, Germany.

出版信息

Biology (Basel). 2023 Jul 22;12(7):1032. doi: 10.3390/biology12071032.

Abstract

Several cues for a directional migration of colorectal cancer cells were identified as being crucial in tumor progression. However, galvanotaxis, the directional migration in direct-current electrical fields, has not been investigated so far. Therefore, we asked whether direct-current electrical fields could be used to mobilize colorectal cancer cells along field vectors. For this purpose, five patient-derived low-passage cell lines were exposed to field strengths of 150-250 V/m in vitro, and migration along the field vectors was investigated. To further study the role of voltage-gated calcium channels on galvanotaxis and intracellular signaling pathways that are associated with migration of colorectal cancer cells, the cultures were exposed to selective inhibitors. In three out of five colorectal cancer cell lines, we found a preferred cathodal migration. The cellular integrity of the cells was not impaired by exposure of the cells to the selected field strengths. Galvanotaxis was sensitive to inhibition of voltage-gated calcium channels. Furthermore, signaling pathways such as AKT and MEK, but not STAT3, were also found to contribute to galvanotaxis in our in vitro model system. Overall, we identify electrical fields as an important contributor to the directional migration of colorectal cancer cells.

摘要

已确定几种促使结肠癌细胞定向迁移的线索在肿瘤进展中至关重要。然而,直流电场中的定向迁移即趋电现象,迄今为止尚未得到研究。因此,我们探讨了直流电场是否可用于促使结肠癌细胞沿电场矢量移动。为此,将五种源自患者的低传代细胞系在体外暴露于150 - 250 V/m的场强下,并研究其沿电场矢量的迁移情况。为进一步研究电压门控钙通道在趋电现象以及与结肠癌细胞迁移相关的细胞内信号通路中的作用,将培养物暴露于选择性抑制剂中。在五种结肠癌细胞系中的三种中,我们发现细胞存在向阴极的优先迁移。细胞暴露于选定的场强下,其细胞完整性未受损害。趋电现象对电压门控钙通道的抑制敏感。此外,在我们的体外模型系统中还发现,诸如AKT和MEK等信号通路而非STAT3信号通路也对趋电现象有作用。总体而言,我们确定电场是结肠癌细胞定向迁移的一个重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eaa/10376471/2bdb051798ed/biology-12-01032-g001.jpg

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