J Cachexia Sarcopenia Muscle (2012) 3:37–43 DOI 10.1007/s13539-011-0049-z ORIGINAL ARTICLE Myostatin blockage using actRIIB antagonism in mice bearing the Lewis lung carcinoma results in the improvement of muscle wasting and physical performance Sílvia Busquets & Míriam Toledo & Marcel Orpí & David Massa & Maria Porta & Eva Capdevila & Núria Padilla & Valentina Frailis & Francisco J. López-Soriano & H. Q. Han & Josep M. Argilés Received: 30 July 2011 / Accepted: 28 October 2011 / Published online: 8 November 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Background Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation. Methods The aim of this investigation was to examine the effect of the soluble receptor antagonist of myostatin (sActRIIB) in cachectic tumor-bearing animals analyzing changes in muscle proteolysis and in quality of life. Results Administration of sActRIIB resulted in an improve- ment in body and muscle weights. Administration of the soluble receptor antagonist of myostatin also resulted in an improvement in the muscle force. Conclusions These results suggest that blocking myostatin pathway could be a promising therapeutic strategy for the treatment of cancer cachexia. S. Busquets : M. Toledo : M. Orpí : D. Massa : M. Porta : E. Capdevila : N. Padilla : V. Frailis : F. J. López-Soriano : J. M. Argilés Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain S. Busquets : F. J. López-Soriano : J. M. Argilés Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain H. Q. Han Departments of Metabolic Disorders and Protein Science, Amgen Research, Thousand Oaks, CA 91320, USA S. Busquets (*) Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain e-mail: silviabusquets@ub.edu Keywords Myostatin . Cancer cachexia . Skeletal muscle . Physical activity . Muscle force . Ubiquitin 1 Introduction Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss (at least 5%), muscle and adipose tissue wasting and inflammation, being often associated with anorexia [1]. The abnormalities associated with cachexia include alterations in carbohydrate, lipid, and protein metabolism [1–3]. In advanced malignant diseases, cachexia appears to be one of the most common systemic manifestations. The presence of cachexia always implies a poor prognosis, having a great impact on the patients' quality of life and survival [4]. Several important molecular mechanisms have been shown to be involved in the increased muscle catabolism observed in cancer-induced cachexia, such as greater ubiquitin–proteasome-dependent proteolysis, apoptosis, and activation of uncoupling proteins [2, 5–7]. Interaction of these mechanisms leads to muscle-mass loss by promoting protein and DNA breakdown and energy inefficiency. Myostatin, also known as GDF-8 (growth and differen- tiation factor-8), is a member of the TGF-b superfamily of secreted growth factors and is a negative regulator of skeletal muscle development [8–10]. During embryogenesis, myostatin expression is restricted to developing skeletal muscles, but the protein is still expressed and secreted by skeletal muscles in adulthood [11, 12]. Mice and cattle with genetic deficiencies in myostatin exhibit dramatic increases in skeletal muscle mass, therefore supporting the role of myostatin in suppressing muscle growth [13]. Myostatin acts systemically (it is produced in muscle, adipose tissue, and