LOSS IN MUSCLE OXIDATIVE PHENOTYPE IN LEWIS LUNG CARCINOMA-INDUCED CANCER-CACHEXIA
Haley N. McCarver1, Jacob L. Brown1, Megan E. Rosa1, David E. Lee1, Richard A. Perry1 Jr., Lemuel A. Brown1, Michael P. Wiggs2, Tyrone A. Washington1, Nicholas P. Greene1. 1University of Arkansas, Fayetteville, 2University of Texas at Tyler.
Cancer is one of the leading causes of death across the world. Cancer-cachexia is a serious complication induced by cancer resulting in whole body muscle wasting. In fact, cancer-cachexia is responsible for up to 40% of cancer related deaths depending on the type of carcinoma. Underlying mechanisms of cancer-cachexia are not well understood; however, a loss in oxidative metabolism in skeletal muscle is apparent in cancer-cachexia. Therefore, mitochondria degeneration in muscle cells may be an underlying cause of cancer-cachexia that ultimately leads to patient death. PURPOSE: To examine oxidative phenotype of skeletal muscle in tumor bearing mice in cancer-cachexia. METHODS: Mice were implanted with Lewis Lung Carcinoma (LLC) or sham phosphate buffered saline (PBS) at 8 weeks of age. The tumor was allowed to progress for 4 weeks. Tibialis Anterior muscle was extracted and snap frozen in optimum cutting temperature compound (OCT). 10 µM cross sections were cut and stained for Succinate dehydrogenase (SDH) to analyze the percent of oxidative muscle fibers. Slides were fixed with a glycerol based mounting medium and imaged using a Nikon microscope at 20X objective. Percent SDH positive fibers were analyzed by counting SDH+ (purple) and SDH- muscle fibers. RESULTS: Tibialis Anterior weight decreased approximately 10% in LLC mice when compared to PBS control mice. We observed a decrease from 65% SDH + oxidative phenotype in PBS group to a 40% SDH+ oxidative phenotype in the muscle fibers in tumor bearing mice. CONCLUSION: LLC in mice may promote a cellular energy crisis induced by a decrease in skeletal muscle oxidative phenotype likely tied to a loss in muscle mitochondrial content. Energy stress promotes atrophic signaling in myofibers, leading to cachexia. Based on these findings, promoting the oxidative phenotype and hence the mitochondrial network could be a potential theraputic target to treat cancer-cachexia.
McCarver, HN; Brown, JL; Rosa, ME; Lee, DE; Perry Jr., RA; Brown, LA; Wiggs, MP; Washington, TA; and Greene, NP
"LOSS IN MUSCLE OXIDATIVE PHENOTYPE IN LEWIS LUNG CARCINOMA-INDUCED CANCER-CACHEXIA,"
International Journal of Exercise Science: Conference Proceedings: Vol. 11
, Article 43.
Available at: http://digitalcommons.wku.edu/ijesab/vol11/iss4/43
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