Cancer-induced cachexia describes a multi-factorial disease condition characterized by massive loss of adipose tissue and skeletal muscle mass. It is believed to be responsible for up to 30% of cancer-related deaths in humans. Schäfer et al. develop and apply cellular high throughput cardiomyocyte phenotyping to test for the cachexia-inducing capacities of a newly defined set of tumor-borne signaling mediators. These cachexokines are both necessary and sufficient to trigger cardiac atrophy and metabolic dysfunction in cardiomyocytes. As a prototype, Ataxin-10 is sufficient to cause cachectic cardiac phenotypes and to signal the existence of cachexia by its serum levels in murine and human model systems as well as in pancreatic cancer patients.
The images show immunofluorescence staining of α-actinin in neonatal rat cardiomyocytes. Exposure to conditioned supernatants from c26 colon cancer cell lines triggers a substantial reduction of cardiomyocyte size.