Metabolic alteration and muscle dysfunction in mice with breast cancer

• Breast cancer accounts for ~25% of diagnosed cancer types in woman [1]. Decreased physical fitness and muscle weakness are common complications in patients with breast cancer. In cancer, muscle weakness has traditionally been linked to muscle wasting and significant weight loss (cachexia) [2]. However, muscle weakness is present in non-cachectic, weight-stable patients with breast cancer [3]. In fact, cancer-induced muscle dysfunction is a broad clinical challenge that is not restricted to palliative or advanced stage patients, but also observed in newly diagnosed patients with low tumor burden [4]. Further, with the breast cancer treatment improving, it is important to take a look on the patients quality of life [5]. However, little is known about the features underlying breast cancer-induced muscle impairments and no drug preventing cancer-induced muscle weakness is clinically proven. Here we aim at characterizing the metabolic status and the muscle function in mice with breast cancer.The breast cancer mouse-model MMTV-PyMT (PyMT) used here, is characterized by an early onset of mammary cancer (from 5 weeks of age) and follows a similar progression pattern as the one observed in human patients [6]. Soleus muscle from PyMT mice exhibited ~30% lower specific force (kN/m2) than soleus muscle from wildtype (WT) mice (n=28-29, p ≤ 0.05, mice were 12 week old at sacrifice). There were no significant differences in muscle mass, fiber size or fiber type distribution between PyMT and WT muscle. Furthermore, there were no differences in glycogen content (μg/g muscle) in soleus muscle from PyMT and WT mice. Simultaneous measurement of numerous parameters (e.g. oxygen consumption (VO2), carbon dioxide production (VCO2), and food and water intake) was carried out using comprehensive lab animal monitoring system (CLAMS) to gain insight into the metabolic status of the mice. The mice were monitored over a week and the average respiratory exchange ratio (RER = CO2production: O2 uptake) were significantly differed between PyMT and WT mice, with mean PyMT RER of 0.95±0.01 and WT RER of 1.0±0.01 (mean data +/-SEM, n=8, p<0.001). Thus, indicative that PyMT have an altered metabolism towards fatty acid utilization.In summary, soleus muscles are weaker and the whole-body metabolism appears altered in mice with breast cancer as compared with healthy control mice. Gene and molecular analysis are currently being performed to further assess mitochondrial and glucose metabolism. Nevertheless, further studies are needed to gain insight into cancer-derived factors that contributes to skeletal muscle dysfunction and altered metabolism.1. Jemal, A., et al., Cancer statistics, 2008. CA Cancer J Clin, 2008. 58(2): p. 71-96.2. Johns, N., N.A. Stephens, and K.C. Fearon, Muscle wasting in cancer. Int J Biochem Cell Biol, 2013. 45(10): p. 2215-29.3. Klassen, O., et al., Muscle strength in breast cancer patients receiving different treatment regimes. Journal of Cachexia, Sarcopenia and Muscle, 2017. 8(2): p. 305-316.4. Villasenor, A., et al., Prevalence and prognostic effect of sarcopenia in breast cancer survivors: the HEAL Study. J Cancer Surviv, 2012. 6(4): p. 398-406.5. Perry, S., T.L. Kowalski, and C.H. Chang, Quality of life assessment in women with breast cancer: benefits, acceptability and utilization. Health Qual Life Outcomes, 2007. 5: p. 24.6. Fantozzi, A. and G. Christofori, Mouse models of breast cancer metastasis. Breast Cancer Res, 2006. 8(4): p. 212.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

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