Abstract
BackgroundElectrotaxis is the movement of adherent living cells in response to a direct current (dc) electric field (EF) of physiological strength. Highly metastatic human lung cancer cells, CL1–5, exhibit directional migration and orientation under dcEFs. To understand the transcriptional response of CL1–5 cells to a dcEF, microarray analysis was performed in this study.Methodology/Principal FindingsA large electric-field chip (LEFC) was designed, fabricated, and used in this study. CL1–5 cells were treated with the EF strength of 0mV/mm (the control group) and 300mV/mm (the EF-treated group) for two hours. Signaling pathways involving the genes that expressed differently between the two groups were revealed. It was shown that the EF-regulated genes highly correlated to adherens junction, telomerase RNA component gene regulation, and tight junction. Some up-regulated genes such as ACVR1B and CTTN, and some down-regulated genes such as PTEN, are known to be positively and negatively correlated to cell migration, respectively. The protein-protein interactions of adherens junction-associated EF-regulated genes suggested that platelet-derived growth factor (PDGF) receptors and ephrin receptors may participate in sensing extracellular electrical stimuli. We further observed a high percentage of significantly regulated genes which encode cell membrane proteins, suggesting that dcEF may directly influence the activity of cell membrane proteins in signal transduction.Conclusions/SignificanceIn this study, some of the EF-regulated genes have been reported to be essential whereas others are novel for electrotaxis. Our result confirms that the regulation of gene expression is involved in the mechanism of electrotactic response.
Highlights
Electrotaxis, known as galvanotaxis, is the movement of organisms or cells in response to an electric field (EF)
large electric-field chip (LEFC) and EF stimulation To build up an EF with the strength of 300mV/mm in the cell culture region, the current flow of 696 mA was introduced into the LEFC by applying the voltage of about 21V on the electrodes (Figure 2)
20–30 mg total RNA is required for one GeneChip, which means that about 106 CL1–5 cells are needed for each replicate
Summary
Electrotaxis, known as galvanotaxis, is the movement of organisms or cells in response to an electric field (EF). Physiological EF exists extracellularly, such as in wound, embryo’s skin, and ducts [1,2]. It may exist in the interface between tumors and normal tissues [3,4]. Several types of cancer cells such as prostate cancer cells, breast cancer cells, and lung cancer cells, are known to migrate directionally under dcEF, and the degree of electrotaxis of these cancer cells has been shown to correlate to their metastatic abilities [5,6,7,8]. Electrotaxis is the movement of adherent living cells in response to a direct current (dc) electric field (EF) of physiological strength. To understand the transcriptional response of CL1–5 cells to a dcEF, microarray analysis was performed in this study
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