Metabolic features of tumor-derived extracellular vesicles: challenges and opportunities

Abstract

Tumor-derived extracellular vesicles (TDEVs) play crucial roles in intercellular communication both in the local tumor microenvironment and systemically, facilitating tumor progression and metastatic spread. They carry a variety of molecules with bioactive properties, such as nucleic acids, proteins and metabolites, that trigger different signaling processes in receptor cells and induce, among other downstream effects, metabolic reprogramming. Interestingly, the cargo of TDEVs also reflects the metabolic status of the producing cells in a time- and context-dependent manner, providing information on the functionality and state of those cells. For these reasons, together with their ability to be detected in diverse biofluids, there is increasing interest in the study of TDEVs, particularly their metabolic cargo, as diagnostic and prognostic tools in cancer management. This review presents a compilation of metabolism-related molecules (enzymes and metabolites) described in cancer extracellular vesicles (EVs) with potential use as cancer biomarkers, and discusses the challenges arising in this rapidly evolving field.

Keywords: Extracellular vesicles; biomarkers; cancer; metabolism; metabolites.

Figure 1

Biomarkers of TDEVs described in four representative cancer types. Specific biomarkers (proteins, nucleic acids and metabolites) as well as general EV-related biomarkers have been included for breast, colorectal, pancreatic, and prostate cancers. Lipids: CE: cholesteryl esters; DAG: diacylglycerol; FA: fatty acids; GL: glycolipids; GP: glycerophospholipids. Glyco-PS: glycophosphosphingolipids; Lyso-PC: lysophospatidylcholine; P: propionate; PC: phosphatidylcholine; PE: phosphatidyletanolamine; PS: phosphatidylserine; SM: sphingomyelin; SP: sphingolipids; ST: sterols; TDEVs: tumor-derived extracellular vesicles.