Protein Synthesis throughout the Progression of Cancer Cachexia in Tumor‐Bearing Mice

Abstract

Cancer cachexia occurs in approximately 80 percent of cancer patients and is a key contributor to cancer‐related death. The mechanisms controlling development of tumor‐induced muscle wasting are not fully elucidated. Specifically, the progression of cancer cachexia is underexplored. We have previously reported that muscle wasting occurs 4 wks following tumor implantation in these mice.PurposeTo examine the rate of muscle protein synthesis throughout the progression of cancer cachexia in tumor‐bearing mice.MethodsLewis Lung Carcinoma (LLC) was injected into the hind‐flank of C57BL6/J mice at 8 wks age with tumor allowed to develop for 1, 2, 3, or 4 wks and compared to PBS injected control. PBS control animals were age matched to the 4 wk tumor bearing group. Cumulative fractional protein synthetic rates (FSR) were determined using deuterium oxide (2H20). Briefly, a (20 μL/g body weight) bolus priming dose of deuterium oxide was injected intraperitoneally approximately 24 hours before tissue collection. Drinking water was thereafter supplemented with 4% deuterium oxide in order to maintain the plasma pool of deuterium oxide. Fractional synthetic rate (FSR) of mixed muscle fraction (soluble, mitochondria, sarcolemmal, and contractile) and myofibrillar (contractile) rich fraction from gastrocnemius muscle were measured us a GC/MS. Data were analyzed by one‐way ANOVA. When significant F‐ratios were found, a SNK post hoc was used to compare differences between experimental groups. Significance was established at p<0.05.ResultsPlasma enrichment of 2H20 for all groups was 2.91 ± 0.073% and no significant differences existed in means between groups. Mixed muscle FSR remained consistent in 1 wk and 2 wk animals and was ~40% lower 4 wks following tumor implantation (p<0.05) when compared to PBS control. The myofibrillar rich fraction of FSR followed a similar pattern, but changes did not reach statistical significance between groups.ConclusionsThese data indicate muscle protein synthesis decreases concomitantly with muscle loss and may be a major contributor of cancer cachexia in tumor‐bearing mice. More research needs to be conducted to analyze the mechanism for the loss of protein synthesis in cachectic mice.Support or Funding InformationThis study was supported by The Arkansas Bioscience Institute and National Institutes of Health R15AR069913.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.