Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/29/2019
Publication Date: 6/12/2019
Citation: Yan, L., Nielsen, F., Sundaram, S., Cao, J.J. 2019. Dietary selenium supplementation does not attenuate mammary tumorigenesis-mediated bone loss in male MMTV-PyMT mice. Biological Trace Element Research. https://doi.org/10.1007/s12011-019-01767-7.
Interpretive Summary: Wasting occurs during the progression of breast cancer. It is characterized by weight loss and multi-organ failures including bone loss. Wasting is a risk factor for cancer-related death. Prevention of wasting can be a useful adjuvant in improving the quality of cancer treatment and prevention. Selenium is an essential nutrient to humans with demonstrated capability of breast cancer prevention. We investigated the effect of a synthetic selenium compound, methylseleninic acid (MSeA), on breast cancer-mediated bone loss in a mouse model of male breast cancer, which is an aggressive disease with poor prognosis. We found that consumption of a diet supplemented with MSeA inhibited the growth of breast tumors, but it did not prevent the bone loss in this model of breast cancer. The lack of effect in preventing bone loss by MSeA may be due to its inhibition of estrogen, which plays a key role in promoting breast cancer growth but also is needed in maintaining bone health. Findings from this study demonstrate the protection of selenium against breast cancer and suggest the need of additional strategies in combination with selenium supplementation to achieve the goal of preventing breast cancer and its associated bone wasting.
Technical Abstract: Bone wasting occurs during the progression of breast cancer and contributes to breast cancer mortality. We evaluated the effect of methylseleninic acid (MSeA), an anti-carcinogenic form of selenium, on bone microstructural changes in the presence of mammary tumors in a male breast cancer model of mouse mammary tumor virous-polyomavirus middle T-antigen (MMTV-PyMT). In this study, we performed micro-computed tomographic analysis of femurs and vertebrae collected from a study showing that dietary supplementation with MSeA (4 mg/kg) reduces mammary tumorigenesis in male mice. Compared to age-matched, non-tumor-bearing mice (MMTV-PyMT negative), the presence of mammary tumors significantly reduced the bone volume fraction, trabecular thickness, and bone mineral density while increasing the structure model index in femurs, but not in vertebrae. Moreover, mammary tumorigenesis decreased plasma concentrations of osteocalcin. MSeA supplementation did not affect these changes in MMTV-PyMT mice. In conclusion, mammary tumorigenesis caused bone loss in MMTV-PyMT mice; however, dietary supplementation with MSeA did not attenuate mammary tumor-associated bone loss in this model of male breast cancer.