Cachexia does not induce loss of myonuclei or muscle fibers during xenografted prostate cancer in mice.

AIM: Cachexia is a severe wasting disorder involving loss of body- and muscle mass reducing survival and quality of life in cancer patients. We aim at determining if cachexia is a mere perturbation of the protein balance or if the condition also involves a degenerative loss myonuclei within the fiber syncytia or loss of whole muscle fibers.

METHODS: We induced cachexia by xenografting PC3 prostate cancer cells in nu/nu mice. Six weeks later, we counted myonuclei by in vivo microscopic imaging of single live fibers in the extensor digitorum longus muscle (EDL), and the EDL, soleus and tibialis anterior muscles were also harvested for ex vivo histology.

RESULTS: The mice lost on average 15% of the whole-body weight. The muscle wet weight of the glycolytic, fast EDL was reduced by 14%, the tibialis anterior by 17%, and the slow, oxidative soleus by 6%. The fiber cross sectional area in the EDL was reduced by 21% with no loss of myonuclei or any significant reduction in the number of muscle fibers. TUNEL-positive nuclei or fibers with embryonic myosin were rare both in cachectic and control muscles, and hematoxylin-eosin staining revealed no clear signs of muscle pathology.

CONCLUSION: The data suggest that the cachexia induced by xenografted prostate tumors induces a pronounced atrophy not accompanied by a loss of myonuclei or a loss of muscle fibers. Thus, stem-cell related treatment might not be beneficial, and the quest for treatment options should rather focus on intervening with intracellular pathways regulating muscle fiber-size. This article is protected by copyright. All rights reserved.