Concurrent muscle and bone deterioration in a murine model of cancer cachexia

Eunhi Choi, Kadir Carruthers, Li Zhang, Nathan Thomas, Ricardo A. Battaglino, Leslie R. Morse, Jeffrey J. Widrick

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Cachexia is defined as an excessive, involuntary loss of fat and lean tissue. We tested the validity of the Lewis lung carcinoma (LLC) as a model of cancer cachexia and examined its effect on the two major lean tissue components, skeletal muscle and bone. LLC cells (0.75 9 106) were injected into the left thigh of C57BL/6 mice. Control mice received an equal volume injection of growth media. Tumors were observed in all LLC-injected animals 21 and 25 days post inoculation. LLC-injected animals showed significant reductions in fat and lean mass despite having the same average daily caloric intake as media-treated mice. Global bone mineral density (BMD) had fallen by 5% and 6% in the LLC animals at 21 and 25 days, respectively, compared to a BMD increase of 5% in the 25-day media-treated animals. Extensor digitorum longus (EDL) muscles (isolated from the noninjected hindlimb) showed earlier and quantitatively greater losses in mass, physiological cross-sectional area (pCSA), and tetanic force compared to soleus muscles from the same hindlimb. By the 25th day post-LLC inoculation, EDL force/pCSA was reduced by 19% versus media treatment. This loss in specific force was not trivial as it accounted for about one-third of the reduction in EDL absolute force at this time point. Muscle strips dissected from the diaphragm of LLC mice also exhibited significant reductions in force/pCSA at day 25. We conclude that LLC is a valid model of cachexia that induces rapid losses in global BMD and in limb and respiratory muscle function.

Original languageEnglish (US)
Article numbere00144
Pages (from-to)1-9
Number of pages9
JournalPhysiological Reports
Volume1
Issue number6
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported in part by National Institutes of Health (NIH) grant L30 HD056721 to L. R. M.

Keywords

  • Body composition
  • Bone mineral density
  • Muscle function
  • Muscle strength

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