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 language | English (US) |
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Article number | e00144 |
Pages (from-to) | 1-9 |
Number of pages | 9 |
Journal | Physiological Reports |
Volume | 1 |
Issue number | 6 |
DOIs | |
State | Published - Jan 1 2013 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was supported in part by National Institutes of Health (NIH) grant L30 HD056721 to L. R. M.
Publisher Copyright:
© 2013 The Authors.
Keywords
- Body composition
- Bone mineral density
- Muscle function
- Muscle strength