title: Concurrent muscle and bone deterioration in a murine model of cancer cachexia.
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.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts ; Deparment of Physical Medicine and Rehabilitation, Hallym University College of Medicine Gangwon-do, South Korea.
authors.forename: Eunhi
authors.initials: E
authors.lastname: Choi
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts.
authors.forename: Kadir
authors.initials: K
authors.lastname: Carruthers
authors.affiliation: Forsyth Institute Cambridge, Massachusetts.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts.
authors.forename: Nathan
authors.initials: N
authors.lastname: Thomas
authors.affiliation: Forsyth Institute Cambridge, Massachusetts.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Battaglino
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts ; Forsyth Institute Cambridge, Massachusetts.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Morse
authors.affiliation: Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School Boston, Massachusetts.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Widrick
keywords: Body composition; bone mineral density; muscle function; muscle strength