Concurrent muscle and bone deterioration in a murine model of cancer cachexia. Issue 6 (7th November 2013)

• Record Type: Journal Article
• Authors: Choi, EunHi; Carruthers, Kadir; Zhang, Li; Thomas, Nathan; Battaglino, Ricardo A.; Morse, Leslie R.; Widrick, Jeffrey J.
• Is Part Of: Physiological reports. Volume 1:Issue 6(2013:Nov.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2013-11-07
• Subjects: Body composition -- bone mineral density -- muscle function -- muscle strength; Physiology -- Periodicals; 571
• DOI: 10.1002/phy2.144
• Languages: English
• ISSNs: 2051-817X

Abstract

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 × 10 6 ) 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. Abstract : e00144 Bone mineral density was significantly reduced in young mice inoculated with the Lewis lung carcinoma. Extensor digitorum longus (EDL) and diaphragm muscles (DIA), but not soleus muscles (SOL), from these animals showed a loss in tetanic force that greatly exceeded the degree of muscle wasting, suggesting an impact of cachexia on cellular mechanisms of contraction in addition to its effect on gross muscle mass. The Lewis lung carcinoma model may be a useful preclinical tool for investigating cachexia‐related changes to the musculoskeletal systems.