Tumor burden negatively impacts protein turnover as a proteostatic process in non-cancerous liver, heart, and muscle, but not brain

Abstract

Cancer survivors are more susceptible to pathologies such as hypertension, liver disease, depression, and coronary artery disease when compared to individuals who have never been diagnosed with cancer. Therefore, it is important to understand how tumor burden negatively impacts non-tumor bearing tissues that may impact future disease susceptibility. We hypothesized that the energetic costs of a tumor would compromise proteostatic maintenance in other tissues. Therefore, the purpose of this study was to determine if tumor burden changes protein synthesis and proliferation rates in heart, brain, and liver. One million Lewis Lung Carcinoma (LLC) cells or Phosphate Buffered Saline (PBS, sham) were injected into the hind-flank of female mice at ~4.5 months of age, and the tumor developed for 3 weeks. Rates of proliferation and protein synthesis were measured in heart, brain, liver, and tumor tissue. Compared to Sham, rates of protein synthesis (structural/nuclear, cytosolic, mitochondrial, and collagen) relative to proliferation were lower in the heart and liver of LLC mice, but higher in the brain of LLC mice. In the tumor tissue the ratio of protein synthesis to DNA synthesis was approximately 1.0 showing that protein synthesis in the tumor was used for proliferation with little proteostatic maintenance. We further provide evidence that the differences in tissue responses may be due to energetic stress. We concluded that the decrease in proteostatic maintenance in liver, heart and muscle might contribute to the increased risk of disease in cancer survivors.