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Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?

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Abstract

The Na+/I− symporter (NIS) is a transmembrane glycoprotein that mediates iodide uptake into thyroid follicular cells and serves as the molecular basis of radioiodine imaging and therapy for thyroid cancer patients. The finding that NIS protein is present in 80–90% of breast tumors suggests that breast cancer patients may also benefit from NIS-mediated radionuclide imaging and targeted therapy. However, only 17–25% of NIS-positive breast tumors have detectable radionuclide uptake activity. The discrepancy between NIS expression and radionuclide uptake activity is most likely contributed by variable cell surface NIS protein levels. Apart from the prevalent view that NIS cell surface trafficking impairments account for the variability, our current study proposes that differential levels of NIS expression may also account for variable cell surface NIS levels among breast tumors. We address the need to confirm the identity of intracellular NIS staining to reveal the mechanisms underlying variable cell surface NIS levels. In addition, we warrant a quantitative correlation between cell surface NIS levels and radionuclide uptake activity in patients such that the cell surface NIS levels required for radionuclide imaging can be defined and the defects impairing NIS activity can be recognized.

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Acknowledgments

This work was supported by the NIH NCI R21 CA10887 (to S.M.J.). Samples were obtained from the Spielman Breast Cancer Tissue Bank, Human Cancer Genetics Program and Comprehensive Cancer Center, The Ohio State University. We thank Susie Jones for her assistance in immunohistochemical staining as well as Douangsone Vadysirisack and Yu-Yu Liu for their assistance in preparation of the manuscript.

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Authors and Affiliations

  1. Integrated Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, 43210, USA

    S. J. Beyer

  2. Department of Pathology, The Ohio State University, Columbus, OH, 43210, USA

    R. E. Jimenez

  3. Division of Hematology and Oncology, The College of Medicine, The Ohio State University, Columbus, OH, 43210, USA

    C. L. Shapiro

  4. Department of Biochemistry, School of Dentistry and IHBR, Kyungpook National University, Daegu, South Korea

    J. Y. Cho

  5. Department of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH, 43210, USA

    S. M. Jhiang

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  1. S. J. Beyer
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  2. R. E. Jimenez
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  3. C. L. Shapiro
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  4. J. Y. Cho
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  5. S. M. Jhiang
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Correspondence to S. M. Jhiang.

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Beyer, S.J., Jimenez, R.E., Shapiro, C.L. et al. Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?. Breast Cancer Res Treat 115, 205–212 (2009). https://doi.org/10.1007/s10549-008-0059-5

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  • DOI: https://doi.org/10.1007/s10549-008-0059-5

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