Comparative profiling reveals tumor-specific metabolic adaptations in brain metastases versus glioblastoma, indicating targets for subtype-tailored therapies.
Key Points
To determine the metabolic differences between primary glioblastoma and brain metastases originating from breast and lung cancers in order to uncover targetable adaptive pathways.
Conducted steady-state metabolic profiling using LC-MS for polar metabolites and GC-MS for non-polar metabolites on resected fresh-frozen glioblastoma and breast and lung brain metastases.
Assessed metabolic pathway utilization via 13C6-glucose and 13C6-palmitate isotope tracing in patient-derived 2D cell cultures and ex vivo tumour slices.
Breast cancer brain metastases demonstrated elevated free fatty acids, marked PLIN2 lipid droplet staining, and upregulated FASN and ACC1 expression compared to glioblastoma, reflecting increased de-novo lipogenesis.
Lung cancer brain metastases showed significantly elevated levels of GABA and glutamine relative to glioblastoma, indicating metabolic adaptation driven by neuronal and glial neurotransmitter pathways.