The growth of murine breast cancer cells in dystrophic mice
Meaney, Mary Patricia
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The American Cancer Society predicted that 230,480 women would be diagnosed with, and 39,520 women would die from breast cancer (BC) in the United States in 2011. While the incidence of female BC has been decreasing, BC remains the second leading cause of cancer death among women in the United States. Cancer cachexia, the cancer-related loss of muscle, affects up to 25% of BC patients and is associated with poor prognosis and decreased quality of life. Alterations to the dystrophin glycoprotein complex (DGC), a transmembrane, multi-subunit protein complex with structural and signaling roles, have been reported in mammary tumors of BC patients and skeletal muscles of cachectic cancer patients. However, this complex is most frequently studied for its role in Duchenne muscular dystrophy (DMD), a severe, progressive muscle wasting disease. Despite the similar alterations reported in these diseases, it is unclear whether alterations in the DGC in one tissue can impact the progression of disease in another. Purpose: The purpose of the studies described in this dissertation was to identify differences in body composition, energy expenditure and plasma cytokine content between the C57BL/10ScSn-Dmdmdx/J (mdx) mouse model of DMD and C57BL/10ScSnJ (BL/10) control mice and to determine whether systemic alteration of the DGC (as observed in the mdx mouse) alters the growth of E0771 murine mammary tumors. Results: There were differences in body composition and plasma cytokine profiles between mdx and BL/10 mice. We also found that, relative to controls, the tumorâ induced increase in cytokines that promote invasion and metastasis was not as severe in mdx mice. Conclusions: This study revealed several differences between mdx and BL/10 mice and provides support for the suggestion that the mdx mouse may not be an accurate model of DMD. In addition, the improved cytokine profile of tumor-bearing mdx mice suggests that the acute phase of DMD may be protective against BC invasion and metastasis. Further research should confirm this effect and determine whether alterations in the DGC of the mdx mouse are directly or indirectly responsible.
- Doctoral Dissertations