Abstract 3380: Cancer usurps skeletal muscle as an energy repository

Abstract

Cancer cells produce energy through aerobic glycolysis, but contributions of host tissues to cancer energy metabolism is unclear. In this study, we aimed to elucidate the cancer-host energy production relationship, in particular, between cancer energy production and host muscle. During the development and progression of colorectal cancer (CRC), expression of the secreted autophagy-inducing stress protein HMGB1 increased in the muscle of tumor-bearing animals. This effect was associated with decreased expression of pyruvate kinase PKM1 and pyruvate kinase activity in muscle via the HMGB1 receptor RAGE. However, muscle mitochondrial energy production was maintained. In contrast, HMGB1 addition to CRC cells increased lactate fermentation. In the muscle, HMGB1 addition induced autophagy by decreasing levels of active mTOR and increasing autophagy-associated proteins, plasma glutamate and 13C-glutamine incorporation into acetyl-CoA. In a mouse model of colon carcinogenesis, a temporal increase in HMGB1 occurred in serum and colonic mucosa with an increase in autophagy associated with altered plasma free amino acids levels, increased glutamine and decreased PKM1 levels. These differences were abolished by administration of an HMGB1 neutralizing antibody. Similar results were obtained in a mouse xenograft model of human CRC. Taken together, our findings suggest that HMGB1 released during tumorigenesis recruits muscle to supply glutamine to cancer cells as an energy source. Citation Format: Yi Luo, Junya Yoneda, Hitoshi Ohmori, Takamitsu Sasaki, Hiroki Kuniyasu. Cancer usurps skeletal muscle as an energy repository. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3380. doi:10.1158/1538-7445.AM2014-3380

Marathon Run-induced Changes in the Erythropoietin-Erythroferrone-Hepcidin Axis are Iron Dependent

“…Furthermore, an increase in the markers of inflammatory response and muscle damage (creatine kinase (CK), leukocytes, neutrophils, and pentraxin 3) was apparent. However, contrary to the expectations, the levels of HMGB1, a pro-inflammatory protein [17], did not increase after the marathon. Finally, transferrin, TIBC and EPO levels increased after the marathon run (Table 2), which may indicate a stress-adaptive response induced by intense running (23,24).…”

Metabolic Profiling of Tumors, Sera, and Skeletal Muscles from an Orthotopic Murine Model of Gastric Cancer Associated-Cachexia

“…Therefore, our results confirm that both hyperlipidemia and hypoglycemia play central roles in cancer cachexia. Free amino acids in blood pool are supplied by either dietary proteins or proteolysis . Given that the food intake of BGC823 mice was not significantly decreased compared to that of controls, the enhanced serum levels of glutamine, glutamate, lysine, leucine, and glycine might reflect the promoted host hypercatabolism in cachectic mice.…”