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

SIMPLE SUMMARY: In colorectal carcinoma, migration of the cancer cells greatly contributes to the progression of the disease. One of the driving factors for a directional migration could be the presence of direct-current electrical fields, which is known as galvanotaxis. To investigate migration of colorectal cancer cells in direct-current electrical fields, we employed five low-passage cell lines that were derived from surgical specimens. In three out of five cell lines, a preferred cathodal migration was determined. Exposure to electrical fields in vitro had no effect on cellular integrity. Furthermore, we found voltage-gated calcium channels crucial in galvanotaxis. Intracellular signaling pathways based on the kinases MEK and AKT were identified as being involved in the migratory phenotype. We conclude that colorectal cancer cells are capable of galvanotactic migration. The directional migration was dependent on calcium influx and activation of central signaling pathways of colorectal cancer. 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.