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Investigating contactless high frequency ultrasound microbeam stimulation for determination of invasion potential of breast cancer cells

Authors

  • Jae Youn Hwang,

    1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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  • Nan Sook Lee,

    1. Department of Physiology and Biophysics, University of Southern California, Los Angeles, California
    2. Keck School of Medicine, University of Southern California, Los Angeles, California
    3. Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California
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  • Changyang Lee,

    1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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  • Kwok Ho Lam,

    1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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  • Hyung Ham Kim,

    1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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  • Jonghye Woo,

    1. Department of Neural and Pain Sciences, University of Maryland, Baltimore, Maryland
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  • Ming-Yi Lin,

    1. Department of Physiology and Biophysics, University of Southern California, Los Angeles, California
    2. Keck School of Medicine, University of Southern California, Los Angeles, California
    3. Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California
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  • Kassandra Kisler,

    1. Department of Physiology and Biophysics, University of Southern California, Los Angeles, California
    2. Keck School of Medicine, University of Southern California, Los Angeles, California
    3. Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California
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  • Hojong Choi,

    1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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  • Qifa Zhou,

    1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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  • Robert H. Chow,

    Corresponding author
    1. Keck School of Medicine, University of Southern California, Los Angeles, California
    2. Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California
    • Department of Physiology and Biophysics, University of Southern California, Los Angeles, California
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  • K. Kirk Shung

    1. Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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Correspondence to: R.H. Chow, 1501 San Pablo Street, ZNI 325, Los Angeles, CA.

ABSTRACT

In this article, we investigate the application of contactless high frequency ultrasound microbeam stimulation (HFUMS) for determining the invasion potential of breast cancer cells. In breast cancer patients, the finding of tumor metastasis significantly worsens the clinical prognosis. Thus, early determination of the potential of a tumor for invasion and metastasis would significantly impact decisions about aggressiveness of cancer treatment. Recent work suggests that invasive breast cancer cells (MDA-MB-231), but not weakly invasive breast cancer cells (MCF-7, SKBR3, and BT-474), display a number of neuronal characteristics, including expression of voltage-gated sodium channels. Since sodium channels are often co-expressed with calcium channels, this prompted us to test whether single-cell stimulation by a highly focused ultrasound microbeam would trigger Ca2+ elevation, especially in highly invasive breast cancer cells. To calibrate the diameter of the microbeam ultrasound produced by a 200-MHz single element LiNbO3 transducer, we focused the beam on a wire target and performed a pulse-echo test. The width of the beam was ∼17 µm, appropriate for single cell stimulation. Membrane-permeant fluorescent Ca2+ indicators were utilized to monitor Ca2+ changes in the cells due to HFUMS. The cell response index (CRI), which is a composite parameter reflecting both Ca2+ elevation and the fraction of responding cells elicited by HFUMS, was much greater in highly invasive breast cancer cells than in the weakly invasive breast cancer cells. The CRI of MDA-MB-231 cells depended on peak-to-peak amplitude of the voltage driving the transducer. These results suggest that HFUMS may serve as a novel tool to determine the invasion potential of breast cancer cells, and with further refinement may offer a rapid test for invasiveness of tumor biopsies in situ. Biotechnol. Bioeng. 2013;110: 2697–2705. © 2013 Wiley Periodicals, Inc.

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