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Dietary Supplementation with Methylseleninic Acid Inhibits Mammary Tumorigenesis and Metastasis in Male MMTV-PyMT Mice

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Abstract

Male breast cancer, which makes up approximately 1% of all breast cancers, is an aggressive disease with poor prognosis. We investigated the effects of dietary supplementation with selenium in the form of methylseleninic acid [(MSeA) 2.5 mg selenium/kg] on mammary tumorigenesis in male MMTV-PyMT mice. The mammary tumor latency was 14.6 weeks for the MSeA-fed group and 13.8 weeks for the controls fed the AIN93G diet (p < 0.05). Dietary supplementation with MSeA, versus the control, resulted in a 72% reduction in tumor progression, a 46% reduction in both final volume and weight of mammary tumors, and a 70% reduction in the number of lung metastases. Mammary tumorigenesis in MMTV-PyMT mice, versus non-tumor-bearing wild-type mice, resulted in significant increases in concentrations of plasminogen activator inhibitor-1, urokinase plasminogen activator, monocyte chemotactic protein-1, and vascular endothelial growth factor, but not aromatase and estrogen, in the plasma. Concentrations of all variables mentioned above in both plasma and mammary tumors were lower in MSeA-fed mice. Mammary tumorigenesis reduced plasma levels of adiponectin compared to non-tumor-bearing controls. Adiponectin concentrations in mammary tumors, but not in plasma, were higher in MSeA-fed mice than in controls. In summary, dietary supplementation with selenium in the form of MSeA inhibits mammary tumorigenesis and its pulmonary metastasis in male MMTV-PyMT mice.

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Acknowledgements

The authors acknowledge the assistance of the following staff: Lana DeMars, Kay Keehr, and Nicole Hollar for technical support, Craig Lacher for selenium analysis, LuAnn Johnson for statistical analysis, James Lindlauf for making animal diets, and the vivarium staff for providing high-quality animal care. Funding for this work was provided by the U.S. Department of Agriculture, Agriculture Research Service, Research Project 5450-51000-045-00D.

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Sundaram, S., Yan, L. Dietary Supplementation with Methylseleninic Acid Inhibits Mammary Tumorigenesis and Metastasis in Male MMTV-PyMT Mice. Biol Trace Elem Res 184, 186–195 (2018). https://doi.org/10.1007/s12011-017-1188-7

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