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Characterization and Separation of Cancer Cells with a Wicking Fiber Device

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Abstract

Current cancer diagnostic methods lack the ability to quickly, simply, efficiently, and inexpensively screen cancer cells from a mixed population of cancer and normal cells. Methods based on biomarkers are unreliable due to complexity of cancer cells, plasticity of markers, and lack of common tumorigenic markers. Diagnostics are time intensive, require multiple tests, and provide limited information. In this study, we developed a novel wicking fiber device that separates cancer and normal cell types. To the best of our knowledge, no previous work has used vertical wicking of cells through fibers to identify and isolate cancer cells. The device separated mouse mammary tumor cells from a cellular mixture containing normal mouse mammary cells. Further investigation showed the device separated and isolated human cancer cells from a heterogeneous mixture of normal and cancerous human cells. We report a simple, inexpensive, and rapid technique that has potential to identify and isolate cancer cells from large volumes of liquid samples that can be translated to on-site clinic diagnosis.

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References

  1. Almendro, V., A. Marusyk, and K. Polyak. Cellular heterogeneity and molecular evolution in cancer. Annu. Rev. Pathol. 8:277–302, 2013.

    Article  CAS  PubMed  Google Scholar 

  2. Becker, F. F., X. B. Wang, Y. Huang, R. Pethig, J. Vykoukal, and P. R. Gascoyne. Separation of human breast cancer cells from blood by differential dielectric affinity. PNAS 92:860–864, 1995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Burg, K. J. L., and D. Brunson. A novel use for capillary channel fibers: enhanced engineered tissue systems. IEEE EMBS Annu. Int. Conf. 2358–2361, 2006.

  4. Byun, S., S. Son, D. Amodei, N. Cermak, J. Shaw, J. Ho, and V. C. Hecht. Characterizing deformability and surface friction of cancer cells. PNAS 110:7580–7585, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Charafe-Jauffret, E., C. Ginestier, F. Iovino, J. Wicinski, N. Cervera, P. Finetti, M.-H. Hur, M. E. Diebel, F. Monville, J. Dutcher, M. Brown, P. Viens, L. Xerri, F. Bertucci, G. Stassi, G. Dontu, D. Birnbaum, and M. S. Wicha. Breast cancer cell lines contain functional cancer stem cells with metastatic capacity and a distinct molecular signature. Cancer Res. 69:1302–1313, 2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cho, R. W., and M. F. Clarke. Recent advances in cancer stem cells. Curr. Opin. Genet. Dev. 18:48–53, 2008.

    Article  CAS  PubMed  Google Scholar 

  7. Crowley, E., F. Di Nicolantonio, F. Loupakis, and A. Bardelli. Liquid biopsy: monitoring cancer-genetics in the blood. Nat. Rev. Clin. Oncol. 10:472–484, 2013.

    Article  CAS  PubMed  Google Scholar 

  8. Hanahan, D., and R. Weinberg. Hallmarks of cancer: the next generation. Cell 144:646–674, 2011.

    Article  CAS  PubMed  Google Scholar 

  9. Harris, J. L., M. Stocum, L. Roberts, C. Jiang, J. Lin, and K. Sprott. Quest for the ideal cancer biomarker: an update on progress in capture and characterization of circulating tumor cells. Drug Dev. Res. 74:138–147, 2013.

    Article  CAS  Google Scholar 

  10. Hilbert, K. J., and R. K. Marcus. Separation of water-soluble polymers using capillary-channeled polymer fiber stationary phases. J. Sep. Sci. 33:3571–3577, 2010.

    Article  CAS  PubMed  Google Scholar 

  11. Hung, L. Y., Y. H. Chuang, H. T. Kuo, C. H. Wang, K. F. Hsu, C. Y. Chou, and G. B. Lee. An integrated microfluidic platform for rapid tumor cell isolation, counting and molecular diagnosis. Biomed. Microdevices 15:339–352, 2013.

    Article  CAS  PubMed  Google Scholar 

  12. Lekka, M., D. Gil, K. Pogoda, J. Dulińska-Litewka, R. Jach, J. Gostek, O. Klymenko, S. Prauzner-Bechcicki, Z. Stachura, J. Wiltowska-Zuber, K. Okoń, and P. Laidler. Cancer cell detection in tissue sections using AFM. Arch. Biochem. Biophys. 518:151–156, 2012.

    Article  CAS  PubMed  Google Scholar 

  13. Li, Q. S., G. Y. H. Lee, C. N. Ong, and C. T. Lim. AFM indentation study of breast cancer cells. Biochem. Biophys. Res. Commun. 374:609–613, 2008.

    Article  CAS  PubMed  Google Scholar 

  14. Li, P., Z. S. Stratton, M. Dao, J. Ritz, and T. J. Huang. Probing circulating tumor cells in microfluidics. Lab Chip 13:602–609, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Magee, J. A., E. Piskounova, and S. J. Morrison. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 21:283–296, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Marcus, R. K., W. C. Davis, B. C. Knippel, L. LaMotte, T. A. Hill, D. Perahia, and J. D. Jenkins. Capillary-channeled polymer fibers as stationary phases in liquid chromatography separations. J. Chromatogr. A 986:17–31, 2003.

    Article  CAS  PubMed  Google Scholar 

  17. Marie-Egyptienne, D. T., I. Lohse, and R. P. Hill. Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance: potential role of hypoxia. Cancer Lett. 341:63–72, 2013.

    Article  CAS  PubMed  Google Scholar 

  18. Nagrath, S., L. V. Sequist, S. Maheswaran, D. W. Bell, P. Ryan, U. J. Balis, R. G. Tompkins, and D. A. Haber. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450:1235–1239, 2007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nelson, D. K., and R. K. Marcus. A novel stationary phase: capillary-channeled polymer (C-CP) fibers for HPLC separations of proteins. J. Chromatogr. Sci. 41:475–479, 2003.

    Article  CAS  PubMed  Google Scholar 

  20. Park, J. P., W. M. Blanding, J. A. Feltracco, and B. W. Booth. Validation of an in vitro model of erbB2+ cancer cell redirection. In Vitro Cell. Dev. Biol. Anim. 51:776–786, 2015.

    Article  CAS  PubMed  Google Scholar 

  21. Pittman, J. J., V. Klep, I. Luzinov, and R. K. Marcus. Extraction of metals from aqueous systems employing capillary-channeled polymer (C-CP) fibers modified with poly(acrylic acid) (PAA). Anal. Methods 2:461–469, 2010.

    Article  CAS  Google Scholar 

  22. Shim, S., M. G. Kim, K. Jo, Y. S. Kang, B. Lee, S. Yang, S.-M. Shin, and J.-H. Lee. Dynamic characterization of human breast cancer cells using a piezoresistive microcantilever. J. Biomech. Eng. 132:104501, 2010.

    Article  PubMed  Google Scholar 

  23. Stanelle, R. D., L. C. Sander, and R. K. Marcus. Hydrodynamic flow in capillary-channel fiber columns for liquid chromatography. J Chromatogr A 1100:68–75, 2005.

    Article  CAS  PubMed  Google Scholar 

  24. Suresh, S. Biomechanics and biophysics of cancer cells. Acta Biomater. 3:413–438, 2010.

    Article  Google Scholar 

  25. Swaminathan, V., K. Mythreye, E. O’Brien, A. Berchuck, G. Blobe, and R. Superfine. Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Res. 71:5075–5080, 2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. van de Stolpe, A., K. Pantel, S. Sleijfer, L. W. Terstappen, and J. M. J. Den Toonder. Circulating tumor cell isolation and diagnostics: toward routine clinical use. Cancer Res. 71(5955–5960):14, 2011.

    Google Scholar 

  27. Wirtz, D., K. Konstantopoulos, and P. Searson. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11:512–522, 2012.

    Article  Google Scholar 

  28. Xu, C., J. F. Langenheim, and W. Y. Chen. Stromal–epithelial interactions modulate cross-talk between prolactin receptor and HER2/Neu in breast cancer. Breast Cancer Res. Treat. 134:157–169, 2012.

    Article  CAS  PubMed  Google Scholar 

  29. Xu, W., R. Mezencev, B. Kim, L. Wang, J. McDonald, and T. Sulchek. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PLoS ONE 7:e46609, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yoon, H. J., T. H. Kim, Z. Zhang, E. Azizi, T. M. Pham, C. Paoletti, J. Lin, N. Ramnath, M. S. Wicha, D. F. Hayes, D. M. Simeone, and S. Nagrath. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat. Nanotechnol. 8:735–742, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yu, M., A. Bardia, B. S. Wittner, S. L. Stott, M. E. Smas, D. T. Ting, S. J. Isakoff, J. C. Ciciliano, M. N. Wells, A. M. Shah, K. F. Concannon, M. C. Donaldson, L. V. Sequist, E. Brachtel, D. Sgroi, J. Baselga, S. Ramaswamy, M. Toner, D. A. Haber, and S. Maheswaran. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339:580–584, 2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhang, W., K. Kai, D. S. Choi, T. Iwamoto, Y. H. Nguyen, H. Wong, M. D. Landis, N. T. Ueno, J. Chang, and L. Qin. Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells. PNAS 109:18707–18712, 2012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zou, Y., and Z. Guo. A review of electrical impedance techniques for breast cancer detection. Med. Eng. Phys. 25:79–90, 2003.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Funding for the work was provided, in part, by the Avon Foundation for Women Grant 02-2013-076 and the Clemson University Hunter Endowment.

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Authors and Affiliations

  1. Department of Bioengineering, Clemson University, Clemson, SC, 29634, USA

    Suzanne M. Tabbaa

  2. Institute for Biological Interfaces of Engineering, Clemson University, Clemson, SC, 29634, USA

    Suzanne M. Tabbaa & Karen J. L. Burg

  3. Department of Mathematical Sciences, Clemson University, Clemson, SC, 29634, USA

    Julia L. Sharp

  4. College of Veterinary Medicine, University of Georgia, 501 D.W. Brooks Drive, Athens, GA, 30602, USA

    Karen J. L. Burg

Authors
  1. Suzanne M. Tabbaa
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  2. Julia L. Sharp
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  3. Karen J. L. Burg
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Correspondence to Karen J. L. Burg.

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Associate Editor Jennifer West oversaw the review of this article.

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Tabbaa, S.M., Sharp, J.L. & Burg, K.J.L. Characterization and Separation of Cancer Cells with a Wicking Fiber Device. Ann Biomed Eng 45, 2933–2941 (2017). https://doi.org/10.1007/s10439-017-1909-2

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  • DOI: https://doi.org/10.1007/s10439-017-1909-2

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