Reduced lung cancer burden by selective immunomodulators elicits improvements in muscle proteolysis and strength in cachectic mice

Salazar Degracia, Anna; Granado-Martínez, Paula; Millán-Sánchez, Aïna; Tang, Jun; Pons-Carreto, Alba; Barreiro Portela, Esther

doi:http://dx.doi.org/10.1002/jcp.28437

Reduced lung cancer burden by selective immunomodulators elicits improvements in muscle proteolysis and strength in cachectic mice

Citation

Salazar-Degracia A, Granado-Martínez P, Millán-Sánchez A, Tang J, Pons-Carreto A, Barreiro E. Reduced lung cancer burden by selective immunomodulators elicits improvements in muscle proteolysis and strength in cachectic mice. J Cell Physiol. 2019 Aug;234(10):18041-52. DOI: 10.1002/jcp.28437

Abstract

Identification of to what extent tumor burden influences muscle mass independently of specific treatments for cancer-cachexia remains to be elucidated. We hypothesized that reduced tumor burden by selective treatment of tumor with immunomodulators may exert beneficial effects on muscle wasting and function in mice. Body and muscle weight, grip strength, physical activity, muscle morphometry, apoptotic nuclei, troponin-I systemic levels, interleukin-6, proteolytic markers, and tyrosine release, and apoptosis markers were determined in diaphragm and gastrocnemius muscles of lung cancer (LP07 adenocarcinoma cells) mice (BALB/c) treated with monoclonal antibodies (mAbs), against immune check-points and pathways (CD-137, cytotoxic T-lymphocyte associated protein-4, programed cell death-1, and CD-19; N = 10/group). Nontreated lung cancer cachectic mice were the controls. T and B cell numbers and macrophages were counted in tumors of both mouse groups. Compared to nontreated cachectic mice, in the mAbs-treated animals, T cells increased, no differences in B cells or macrophages, the variables final body weight, body weight and grip strength gains significantly improved. In diaphragm and gastrocnemius of mAbs-treated cachectic mice, number of apoptotic nuclei, tyrosine release, proteolysis, and apoptosis markers significantly decreased compared to nontreated cachectic mice. Systemic levels of troponin-I significantly decreased in treated cachectic mice compared to nontreated animals. We conclude that reduced tumor burden as a result of selective treatment of the lung cancer cells with immunomodulators elicits per se beneficial effects on muscle mass loss through attenuation of several biological mechanisms that lead to increased protein breakdown and apoptosis, which translated into significant improvements in limb muscle strength but not in physical activity parameters.