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Effects of direct current electric fields on lung cancer cell electrotaxis in a PMMA-based microfluidic device

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Abstract

Tumor metastasis is the primary cause of cancer death. Numerous studies have demonstrated the electrotactic responses of various cancer cell types, and suggested its potential implications in metastasis. In this study, we used a microfluidic device to emulate endogenous direct current electric field (dcEF) environment, and studied the electrotactic migration of non-small cell lung cancer cell lines (H460, HCC827, H1299, and H1975) and the underlying mechanisms. These cell lines exhibited greatly different response in applied dcEFs (2–6 V/cm). While H460 cells (large cell carcinoma) showed slight migration toward cathode, H1299 cells (large cell carcinoma) showed increased motility and dcEF-dependent anodal migration with cell reorientation. H1975 cells (adenocarcinoma) showed dcEF-dependent cathodal migration with increased motility, and HCC827 cells (adenocarcinoma) responded positively in migration speed and reorientation but minimally in migrating directions to dcEF. Activation of MAPK and PI3K signaling pathways was found to be associated with the realignment and directed migration of lung cancer cells. In addition, both Ca2+ influx through activated stretch-activated calcium channels (SACCs) (but not voltage-gated calcium channels, VGCCs) and Ca2+ release from intracellular storage were involved in lung cancer cell electrotactic responses. The results demonstrated that the microfluidic device provided a stable and controllable microenvironment for cell electrotaxis study, and revealed that the electrotactic responses of lung cancer cells were heterogeneous and cell-type dependent, and multiple signals contributed to lung cancer cells electrotaxis.

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Acknowledgements

This work was supported by the Research Grants Council of Hong Kong (CRF Project No. CityU9/CRF/13G; GRF Project No. CityU_11303815), the National Key Scientific Research Program (973 Program No. 2012CB933302), the Knowledge Innovation Program of Shenzhen Municipal Government (Grant No. JCYJ20140419115507575; JCYJ20150601102053070), the Outstanding Young Scholars’ Growth Plan in the Colleges and Universities of Liaoning Province (Grant No. LJQ2015067), and the National Natural Science Foundation of China (Grant No. 81201689).

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Authors and Affiliations

  1. Department of Biomedical Sciences, City University of Hong Kong, 31 To Yuen Street, Kowloon Tong, Hong Kong, 999077, China

    Yaping Li, Tao Xu & Mengsu Yang

  2. Key Laboratory of Biochip Technology, Biotechnology and Health Centre, City University of Hong Kong Shenzhen Research Institute, No.8, Yuexing 1st Road, Nanshan District, Shenzhen, Guangdong, 518057, China

    Yaping Li, Xiaomei Chen & Mengsu Yang

  3. Jinzhou Medical University, No.40, Section 3, Songpo Road, Linghe District, Jinzhou, Liaoning, 121000, China

    Tao Xu

  4. Department of Developmental & Cell Biology, University of California, Irvine, CA, 92697, USA

    Shin Lin

  5. Department of Bioengineering, University of Texas at Arlington, Arlington, TX, 76019, USA

    Michael Cho

  6. Department of Mechanical and Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon Tong, Hong Kong, 999077, China

    Dong Sun

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  1. Yaping Li
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Correspondence to Mengsu Yang.

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Li, Y., Xu, T., Chen, X. et al. Effects of direct current electric fields on lung cancer cell electrotaxis in a PMMA-based microfluidic device. Anal Bioanal Chem 409, 2163–2178 (2017). https://doi.org/10.1007/s00216-016-0162-0

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  • DOI: https://doi.org/10.1007/s00216-016-0162-0

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