Uncovering metabolic signatures in cancer-derived exosomes: LC-MS/MS and NMR profiling

Abstract

Understanding the intricate interplay between cancer metabolism and intercellular communication within the tumour microenvironment (TME) is crucial for advancing cancer diagnostics and therapeutics. In this study, we investigate the metabolites present in exosomes derived from three distinct cancer cell lines: pancreatic cancer (MiaPaCa-2), lung cancer (A549), and glioma (C6). Exosomes were isolated using ultrafiltration and characterized using a combination of techniques including nanoparticle tracking analysis (NTA), electron microscopy (EM), western blotting (WB) and Fourier-transform infrared (FTIR) spectroscopy. Leveraging state-of-the-art metabolomics techniques, including untargeted LC-MS/MS and NMR analyses, we elucidated the metabolic signatures encapsulated within cancer-derived exosomes. Notably, our investigation represents the first exploration of exosomal metabolites from pancreatic and glioma cells, addressing a significant gap in current knowledge. Furthermore, our study investigates the correlation between metabolites derived from different cancer cells, shedding light on potential metabolic interactions within the TME. Through comprehensive analyses, this study provides insights into dysregulated metabolic pathways driving cancer progression and offers novel perspectives on the diagnostic and therapeutic utility of exosomal metabolites. Importantly, common metabolites identified among cancer types suggest potential markers detectable by multiple techniques, enhancing their clinical applicability.