TY - JOUR
T1 - Proteomics analysis of circulating small extracellular vesicles
T2 - Focus on the contribution of EVs to tumor metabolism
AU - Anastasi, Federica
AU - Botto, Asia
AU - Immordino, Benoit
AU - Giovannetti, Elisa
AU - McDonnell, Liam A.
N1 - Funding Information: This work was performed with support of the FPSGrant2020 (LMD and AB), AIRC-IG grant 24444 (EG), and COST Action CA21116-TRANSPAN . Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/10
Y1 - 2023/10
N2 - The term small extracellular vesicle (sEV) is a comprehensive term that includes any type of cell-derived, membrane-delimited particle that has a diameter < 200 nm, and which includes exosomes and smaller microvesicles. sEVs transfer bioactive molecules between cells and are crucial for cellular homeostasis and particularly during tumor development, where sEVs provide important contributions to the formation of the premetastic niche and to their altered metabolism. sEVs are thus legitimate targets for intervention and have also gained increasing interest as an easily accessible source of biomarkers because they can be rapidly isolated from serum/plasma and their molecular cargo provides information on their cell-of origin. To target sEVs that are specific for a given cell/disease it is essential to identify EV surface proteins that are characteristic of that cell/disease. Mass-spectrometry based proteomics is widely used for the identification and quantification of sEV proteins. The methods used for isolating the sEVs, preparing the sEV sample for proteomics analysis, and mass spectrometry analysis, can have a strong influence on the results and requires careful consideration. This review provides an overview of the approaches used for sEV proteomics and discusses the inherent compromises regarding EV purity versus depth of coverage. Additionally, it discusses the practical applications of the methods to unravel the involvement of sEVs in regulating the metabolism of pancreatic ductal adenocarcinoma (PDAC). The metabolic reprogramming in PDAC includes enhanced glycolysis, elevated glutamine metabolism, alterations in lipid metabolism, mitochondrial dysfunction and hypoxia, all of which are crucial in promoting tumor cell growth. A thorough understanding of these metabolic adaptations is imperative for the development of targeted therapies to exploit PDAC's vulnerabilities.
AB - The term small extracellular vesicle (sEV) is a comprehensive term that includes any type of cell-derived, membrane-delimited particle that has a diameter < 200 nm, and which includes exosomes and smaller microvesicles. sEVs transfer bioactive molecules between cells and are crucial for cellular homeostasis and particularly during tumor development, where sEVs provide important contributions to the formation of the premetastic niche and to their altered metabolism. sEVs are thus legitimate targets for intervention and have also gained increasing interest as an easily accessible source of biomarkers because they can be rapidly isolated from serum/plasma and their molecular cargo provides information on their cell-of origin. To target sEVs that are specific for a given cell/disease it is essential to identify EV surface proteins that are characteristic of that cell/disease. Mass-spectrometry based proteomics is widely used for the identification and quantification of sEV proteins. The methods used for isolating the sEVs, preparing the sEV sample for proteomics analysis, and mass spectrometry analysis, can have a strong influence on the results and requires careful consideration. This review provides an overview of the approaches used for sEV proteomics and discusses the inherent compromises regarding EV purity versus depth of coverage. Additionally, it discusses the practical applications of the methods to unravel the involvement of sEVs in regulating the metabolism of pancreatic ductal adenocarcinoma (PDAC). The metabolic reprogramming in PDAC includes enhanced glycolysis, elevated glutamine metabolism, alterations in lipid metabolism, mitochondrial dysfunction and hypoxia, all of which are crucial in promoting tumor cell growth. A thorough understanding of these metabolic adaptations is imperative for the development of targeted therapies to exploit PDAC's vulnerabilities.
KW - Exosome
KW - Extracellular vesicles
KW - Metabolism
KW - Pancreatic ductal adenocarcinoma
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=85171441637&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cytogfr.2023.08.003
DO - https://doi.org/10.1016/j.cytogfr.2023.08.003
M3 - Review article
C2 - 37652834
SN - 1359-6101
VL - 73
SP - 3
EP - 19
JO - Cytokine & Growth Factor Reviews
JF - Cytokine & Growth Factor Reviews
ER -