Lung cancer A549 cells migrate directionally in DC electric fields with polarized and activated EGFRs

Abstract

Endogenous direct-current electric fields (dcEFs) occur in vivo in the form of epithelial transcellular potentials or neuronal field potentials. A variety of cells respond to dcEFs by migrating directionally, and this is termed galvanotaxis. The mechanism by which dcEFs direct cell movement, however, is not yet understood, and the effects on lung cancer cells are entirely unknown. We demonstrated that cultured human lung adenocarcinoma A549 cells migrate toward the cathode in applied dcEFs at 3 V/cm. Fluorescence microscopy showed that both epidermal growth factor receptors (EGFRs) and F-actin are polarized to the cathode. EGFR inhibitors, cetuximab and AG1478, reduced the migration rate and directed motility in dcEFs. Western blots showed that ERK and AKT signaling pathways were prominently promoted by dcEFs. EGFR inhibitors could reduce this promotion but not completely. These data suggest that polarization of EGFRs and the activation of their downstream signals play an important role in the galvanotaxis of A549 cells in dcEFs.

Electrotaxis of oral squamous cell carcinoma cells in a multiple-electric-field chip with uniform flow field

“…These include prostate cancer cells, 16 breast cancer cells, 17 and lung adenocarcinoma cells. 18,19,30 Cancer cells having higher metastatic potential also showed stronger electrotactic response. In this study, it is found that, although HSC-3 migrate faster than CL1-5 (28 lm/h vs. 5 lm/h under EFS ¼ 0 mV/mm), the directedness of HSC-3 is not as significant as that of CL1-5 (þ0.48 vs. À0.76 under EFS ¼ 300 mV/mm).…”

“…The electrotactic directionalities of different cancer cell types also correlate with the TEPs of the corresponding tissues. [15][16][17][18][19] The mechanisms of cell electrotaxis have been investigated over the past few decades but have been found to be complex and differ between cell types. 1 Several models of dcEF detection and signal transduction have been proposed.…”

Electrotaxis of lung cancer cells in ordered three-dimensional scaffolds

“…Lung cancer cell lines CL1-5 and A549 have been shown to migrate with clear directivity under dcEF in traditional 2D environments. 9,10 In our present study, cells were seeded into 3D ordered scaffolds, and their movement under an applied EF of 338 mV/mm was observed. Figs.…”

Modulating chemotaxis of lung cancer cells by using electric fields in a microfluidic device

“…[12][13][14][15][16][17] There have also been a number of microfluidic devices used in the investigation of cell electrotaxis and other responses to dcEFs. 5,9,[18][19][20][21][22][23] It is therefore straightforward to combine the concentration gradients and dcEFs into a single device for quantitative comparisons between the influences of these two stimulations on cancer cell migration. However, because the requirements in the fluidic fields for stable concentration gradients and dcEFs could be different, careful design of the microfluidic channels would be needed for such studies on multiple cues of cell guidance.…”