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DC Electric Fields Direct Breast Cancer Cell Migration, Induce EGFR Polarization, and Increase the Intracellular Level of Calcium Ions

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Abstract

Migration of cancer cells leads to invasion of primary tumors to distant organs (i.e., metastasis). Growing number of studies have demonstrated the migration of various cancer cell types directed by applied direct current electric fields (dcEF), i.e., electrotaxis, and suggested its potential implications in metastasis. MDA-MB-231 cell, a human metastatic breast cancer cell line, has been shown to migrate toward the anode of dcEF. Further characterizations of MDA-MB-231 cell electrotaxis and investigation of its underlying signaling mechanisms will lead to a better understanding of electrically guided cancer cell migration and metastasis. Therefore, we quantitatively characterized MDA-MB-231 cell electrotaxis and a few associated signaling events. Using a microfluidic device that can create well-controlled dcEF, we showed the anode-directing migration of MDA-MB-231 cells. In addition, surface staining of epidermal growth factor receptor (EGFR) and confocal microscopy showed the dcEF-induced anodal EGFR polarization in MDA-MB-231 cells. Furthermore, we showed an increase of intracellular calcium ions in MDA-MB-231 cells upon dcEF stimulation. Altogether, our study provided quantitative measurements of electrotactic migration of MDA-MB-231 cells, and demonstrated the electric field-mediated EGFR and calcium signaling events, suggesting their involvement in breast cancer cell electrotaxis.

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Abbreviations

dcEF:

Direct current electric fields

ECM:

Extracellular matrix

EGFR:

Epidermal growth factor receptor

PDMS:

Polydimethylsiloxane

EI:

Electrotactic index

SEM:

Standard error of the mean

MSD:

Mean square displacement

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Acknowledgments

This Research is supported by Grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canada Foundation for Innovation (CFI), the Manitoba Health Research Council (MHRC), and the University of Manitoba. We thank The Nano Systems Fabrication Laboratory (NSFL) at the University of Manitoba, and the Manitoba Centre for Proteomics and Systems Biology for research support. We thank Saravanan Nandagopal for helping collect chemical reagents, Jing Li and Jiandong Wu for helping with microfluidic device preparation. D.W. thanks MHRC for a postdoctoral fellowship.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Physics and Astronomy, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada

    Dan Wu, Xiuli Ma & Francis Lin

  2. Department of Immunology, University of Manitoba, Winnipeg, MB, R3E 0T5, Canada

    Francis Lin

  3. Department of Biological Sciences, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada

    Francis Lin

  4. Department of Biosystems Engineering, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada

    Francis Lin

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  1. Dan Wu
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Correspondence to Francis Lin.

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Wu, D., Ma, X. & Lin, F. DC Electric Fields Direct Breast Cancer Cell Migration, Induce EGFR Polarization, and Increase the Intracellular Level of Calcium Ions. Cell Biochem Biophys 67, 1115–1125 (2013). https://doi.org/10.1007/s12013-013-9615-7

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