Open AccessConcurrent muscle and bone deterioration in a murine model of cancer cachexia
Author(s) -
Choi EunHi,
Carruthers Kadir,
Zhang Li,
Thomas Nathan,
Battaglino Ricardo A.,
Morse Leslie R.,
Widrick Jeffrey J.
Publication year - 2013
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.1002/phy2.144
Subject(s) - cachexia , medicine , lean body mass , sarcopenia , hindlimb , skeletal muscle , endocrinology , diaphragm (acoustics) , muscle mass , lewis lung carcinoma , thigh , chemistry , anatomy , cancer , body weight , physics , acoustics , loudspeaker , metastasis
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.