Fibrosis is part of the normal wound healing process, and is characterized by injury, inflammation, my ofibroblast activation, matrix deposition and remodeling. Excessive fibrosis is the corner stone of several fatal diseases including heart failure, liver, kidney and lung. The research in Aronheim’s lab is focused on the interplay between heart failure and cancer. Recent, yet unpublished study, show that mice with heart failure and cancer have suppressed cardiac remodeling, reduced cardiac hypertrophy, lower fibrosis and improved cardiac contractile function. The precise molecular mechanisms involved in this process are currently being explored. Here we propose to study another devastating human disease, Duchenne Muscular Dystrophy, using the MDX mouse model.
MDX mice harbor loss of function mutation in the dystrophin gene resulting in cardiac, diaphragm and skeletal muscle fibrosis. Our preliminary data using this model shows that tumor growth in these mice improves muscles fibrosis, and cardiac contractile function. Surprisingly, this effect occurs already one week following cancer implantation. Importantly, we demonstrate that a single injection of serum derived from tumor-bearing mice mimics the tumor effect in the MDX mouse model. Here we propose to study the ability of serum derived from mice implanted with human cancer cell lines and serum derived from patients to suppress fibrosis and ameliorate cardiac contractile function in the MDX mouse model. The results will provide strong clinical relevance and provide a solid basis for the identification of the factor/s involved. In addition, the MDX mouse model may be used as a platform for diagnosis for residual disease in patients.