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Skeletal Muscle Function During the Progression of Cancer Cachexia in the Male ApcMin/+ Mouse.

Authors
  • VanderVeen, Brandon N1
  • Hardee, Justin P1
  • Fix, Dennis K1
  • Carson, James A1
  • 1 1 University of South Carolina.
Type
Published Article
Journal
Journal of Applied Physiology
Publisher
American Physiological Society
Publication Date
Nov 09, 2017
Identifiers
DOI: 10.1152/japplphysiol.00897.2017
PMID: 29122966
Source
Medline
Keywords
License
Unknown

Abstract

While cancer-induced skeletal muscle wasting has been widely investigated, the drivers of cancer-induced muscle functional decrements are only beginning to be understood. Decreased muscle function impacts cancer patient quality of life and health status, and several potential therapeutics have failed in clinical trials due to a lack of functional improvement. Furthermore, systemic inflammation and intrinsic inflammatory signaling's role in the cachectic disruption of muscle function requires further investigation. We examined skeletal muscle functional properties during cancer cachexia and determined their relationship to systemic and intrinsic cachexia indices. Male ApcMin/+ (MIN) mice were stratified by percent body weight loss into weight stable (WS; <5% loss) or cachectic (CX; >5% loss). Age-matched C57BL/6 littermates served as controls. Tibialis anterior (TA) twitch properties, tetanic force, and fatigability were examined in situ. TA protein and mRNA expression were examined in the non-stimulated leg. CX decreased muscle mass, tetanic force (Po), and specific tetanic force (sPo). Whole body and muscle fatigability were increased in WS and CX. CX had slower contraction rates, +dP/dt and -dP/dT, which were inversely associated with muscle STAT3 and P65 activation. STAT3 and P65 activation were also inversely associated with Po. However, STAT3 was not related to sPo or fatigue. Muscle SOCS3 mRNA expression was negatively associated with TA weight, Po, and sPo, but not fatigue. Our study demonstrates that multiple functional deficits that occur with cancer cachexia are associated with increased muscle inflammatory signaling. Notably, muscle fatigability is increased in the MIN mouse before cachexia development.

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