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      Extracellular Vesicles and Their Potential Use in Monitoring Cancer Progression and Therapy: The Contribution of Proteomics

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          Abstract

          Extracellular Vesicles (EVs) are small membrane-enclosed particles released by cells and able to vehiculate information between them. The term EVs categorizes many and different vesicles based on their biogenesis and release pathway, such as exosomes (Exo), ectosomes, or shedding microvesicles (SMVs), apoptotic blebs (ABs), and other EVs subsets, generating a heterogeneous group of components able to redistribute their cargo into the entire organism. Moreover EVs are becoming increasingly important in monitoring cancer progression and therapy, since they are able to carry specific disease biomarkers such as Glypican-1, colon cancer-associated transcript 2, CD63, CD24, and many others. The importance of their biological role together with their heterogeneity prompted researchers to adopt and standardize purification methods able to isolate EVs for characterizing their cargo. In this way, mass spectrometry (MS)-based proteomics approaches are emerging as promising tool for the identification and quantification of EVs protein cargoes, but this technique resulted to be deeply influenced by the low quality of the isolation techniques. This review presents the state-of-the-art of EVs isolation, purification, and characterization for omics studies, with a particular focus to their potential use in monitoring cancer progression and therapy.

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          Most cited references 69

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          Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication.

          Normal and malignant cells shed from their surface membranes as well as secrete from the endosomal membrane compartment circular membrane fragments called microvesicles (MV). MV that are released from viable cells are usually smaller in size compared to the apoptotic bodies derived from damaged cells and unlike them do not contain fragmented DNA. Growing experimental evidence indicates that MV are an underappreciated component of the cell environment and play an important pleiotropic role in many biological processes. Generally, MV are enriched in various bioactive molecules and may (i) directly stimulate cells as a kind of 'signaling complex', (ii) transfer membrane receptors, proteins, mRNA and organelles (e.g., mitochondria) between cells and finally (iii) deliver infectious agents into cells (e.g., human immuno deficiency virus, prions). In this review, we discuss the pleiotropic effects of MV that are important for communication between cells, as well as the role of MV in carcinogenesis, coagulation, immune responses and modulation of susceptibility/infectability of cells to retroviruses or prions.
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            The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins.

            Selective trafficking of membrane proteins to lysosomes for destruction is required for proper cell signalling and metabolism. Ubiquitylation aids this process by specifying which proteins should be transported to the lysosome lumen by the multivesicular endosome pathway. The endosomal sorting complex required for transport (ESCRT) machinery sorts cargo labelled with ubiquitin into invaginations of endosome membranes. Then, through a highly conserved mechanism also used in cytokinesis and viral budding, it mediates the breaking off of the cargo-containing intraluminal vesicles from the perimeter membrane. The involvement of the ESCRT machinery in suppressing diseases such as cancer, neurodegeneration and infections underscores its importance to the cell.
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              Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes

              Using ferritin-labeled protein A and colloidal gold-labeled anti-rabbit IgG, the fate of the sheep transferrin receptor has been followed microscopically during reticulocyte maturation in vitro. After a few minutes of incubation at 37 degrees C, the receptor is found on the cell surface or in simple vesicles of 100-200 nm, in which the receptor appears to line the limiting membrane of the vesicles. With time (60 min or longer), large multivesicular elements (MVEs) appear whose diameter may reach 1-1.5 micron. Inside these large MVEs are round bodies of approximately 50-nm diam that bear the receptor at their external surfaces. The limiting membrane of the large MVEs is relatively free from receptor. When the large MVEs fuse with the plasma membrane, their contents, the 50-nm bodies, are released into the medium. The 50-nm bodies appear to arise by budding from the limiting membrane of the intracellular vesicles. Removal of surface receptor with pronase does not prevent exocytosis of internalized receptor. It is proposed that the exocytosis of the approximately 50-nm bodies represents the mechanism by which the transferrin receptor is shed during reticulocyte maturation.
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                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                JO
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2019
                9 June 2019
                : 2019
                Affiliations
                1Department of Pharmacy, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
                2Analytical Biochemistry and Proteomics Laboratory, Centre on Aging Sciences and Translational Medicine (Ce.S.I-MeT), University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
                3Department of Medical, Oral and Biotechnological Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
                4Department of Medicine and Aging Sciences, University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
                5Cellular and Molecular Biochemistry Laboratory, Centre on Aging Sciences and Translational Medicine (Ce.S.I-MeT), University “G. d'Annunzio” of Chieti-Pescara, Chieti, Italy
                Author notes

                Academic Editor: Reza Izadpanah

                Article
                10.1155/2019/1639854
                6590542
                Copyright © 2019 Maria Concetta Cufaro et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funding
                Funded by: Associazione Italiana per la Ricerca sul Cancro
                Award ID: IG 20043
                Categories
                Review Article

                Oncology & Radiotherapy

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