MyoTumour · A novel role for skeletal muscle in tumour growth and proliferation

Cachexia is a life-threatening condition characterized by a drastic loss in both muscle and adipose tissue, which is associated with several pathologies, including cancer. In cancer patients, its prevalence is of 50-80%, and is the direct cause of at least 20% of cancer-associated deaths. Cachectic patients show lower response rates to chemotherapy and a reduced tolerance to anticancer treatment, being of major clinical relevance. So, while cachexia is clearly of great significance for disease prognosis and survival in general, it is mainly considered a consequence of the presence of the tumour. Tumour-induced muscle wasting is due to the development of “anabolic resistance,” which is the impaired ability of nutrition and exercise to stimulate muscle protein synthesis. There have been results, however, which suggest that prevention or reverting muscle mass can lead to significant improvements of survival and overall well-being of tumour-bearing animals. While these results are suggestive of an important role for skeletal muscle, whether or not this is due to a direct effect on tumour biology is not well-established. The proposed project is based on preliminary results showing that tumour growth and proliferation are affected by activating the anabolic kinase Akt specifically in skeletal muscle in vivo, suggestive of muscle-tumour crosstalk. Follow up experiments performed using a microfluidics system showed that this effect is likely mediated by factors directly released by skeletal muscles, and not through indirect effects, like altering food intake or modulation of the immune system. In the current project, we propose to confirm and further decipher the muscle-tumour crosstalk in vivo. Subsequently, we propose to identify muscle-secreted factors with a microfluidics approach analyzing their effect on multiple tumour cell lines.