Crosstalk between muscle and cancer
In certain cancer-related deaths, respiratory failure is caused by loss of mass from the diaphragm muscle. In addition, both the absence of exercise (bed-ridden state) and the inflammatory state of cachexia could be responsible for the increased muscle protein catabolism that further feed cancer growth. Drugs inhibiting this vicious cycle between muscle and cancer could improve the overall body status of cancer patients and improve their clinical outcome. The EU-funded MUSCLEANDCANCER (Search for novel molecules cross-talking between muscle and cancer with therapeutic potential against cachexia and cancer) project wished to investigate the mechanism of lethal muscle wasting in cancer. In addition, they wanted to understand the potential involvement of specific hormones or muscle-secreted molecules present in the circulation of cancer patients. Researchers set up various in vivo cachectic models of cancer, including colon adenocarcinoma and Lewis lung carcinoma, and performed gene expression analysis of atrophying muscles. In addition, they employed sophisticated imaging technologies to phenotype these cancer-bearing animals. Analysis led to the identification of a subset of genes whose expression was downregulated in cachectic muscles of cancer-bearing rodents, but not in those suffering from diabetes or uraemia. Three of these genes (SDF1, PAK1 and ADCY7) belonged to the CXCR4 pathway and their aberrant expression was confirmed in cancer patients. The clinical relevance of this pathway was further demonstrated when the use of anti-cachexia drugs restored the expression of these genes. Also, experimental overexpression of SDF1 and CXCR4 in muscle significantly reduced muscle wasting. Collectively, the findings of the study support the idea that CXCR4 pathway activation in muscle suppresses the deleterious atrophy associated with cancer. Interventions to restore this molecular axis should help prohibit muscle wasting in cancer patients.
Keywords
Muscle, cancer, cachexia, MUSCLEANDCANCER, SDF1, CXCR4
