Project Details
Projekt
HyperCancer. Investigating the metabolic consequences of muscle-tumour interplay
Applicant
Dr. Maria Rohm
Subject Area
Endocrinology, Diabetology, Metabolism
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 536691227
Cancer is increasingly understood as a systemic metabolic disease, given its ability to impair energy homeostasis and induce skeletal muscle atrophy. These impacts are strongly associated with a worsened disease prognosis. Metabolic dysfunction and tissue wasting in cancer are summarized under the term cancer cachexia. Cancer cachexia strongly impairs quality of life and negatively affects outcomes. Both tumor- and host-derived factors mediate cachexia by re-programming cellular and systemic metabolism. In this context, we have previously identified tumor-secreted proteins and circulating bio-reactive lipids as important molecules influencing different aspects of the disease. Muscle wasting caused by an imbalance of protein synthesis and degradation is considered the major determinant of poor outcomes in cachexia. Our preliminary experiments using metabolic flux analysis have shown that both in vivo in mice and in cell culture co-culture systems, the presence of a tumor alters the metabolic state of muscle. The metabolic reprograming of cachectic muscle can lead to substantial muscle atrophy that is specific to cachexia. HyperCancer aims to apply advanced methods of metabolic research to elucidate the metabolic landscape of cancer-muscle interaction in cachexia in relation to muscle hypertrophy and atrophy. We will address this by studying skeletal muscle hypertrophy and atrophy on three levels as defined by the consortium: level 1: intramuscular metabolism, level 2: metabolite exchange with the circulation, and level 3: inter-organ metabolism and metabolic health; all in the context of metabolic dysfunction in cancer. Specifically, we will (I) measure metabolic fluxes in the tumor-muscle-adipose triangle using co-culture systems, (II) measure metabolic fluxes, glucose homeostasis and organ fate in mice with cancer and muscle atrophy and fluxes in cancer cachectic patients, and (III) reverse atrophy or induce hypertrophy to improve metabolic cancer outcomes. Ultimately, our project will help us understand the metabolic mechanisms that explain how tumors reprogram systemic metabolism in general and skeletal muscle metabolism specifically, causing muscle atrophy, and how metabolic health can be restored by targeting muscle, as basis for future interventions in patients with cancer.
DFG Programme
Research Units
