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      Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

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          Abstract

          Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.

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          Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.

          Christoph Kahlert, Sonia A. Melo, Alexei Protopopov … (2014)
          Exosomes are small vesicles (50-150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.
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            Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.

            J Escola, M Kleijmeer, W Stoorvogel … (1998)
            Association of major histocompatibility complex (MHC) class II molecules with peptides occurs in a series of endocytic vacuoles, termed MHC class II-enriched compartments (MIICs). Morphological criteria have defined several types of MIICs, including multivesicular MIICs, which are composed of 50-60-nm vesicles surrounded by a limiting membrane. Multivesicular MIICs can fuse with the plasma membrane, thereby releasing their internal vesicles into the extracellular space. The externalized vesicles, termed exosomes, carry MHC class II and can stimulate T-cells in vitro. In this study, we show that exosomes are enriched in the co-stimulatory molecule CD86 and in several tetraspan proteins, including CD37, CD53, CD63, CD81, and CD82. Interestingly, subcellular localization of these molecules revealed that they were concentrated on the internal membranes of multivesicular MIICs. In contrast to the tetraspans, other membrane proteins of MIICs, such as HLA-DM, Lamp-1, and Lamp-2, were mainly localized to the limiting membrane and were hardly detectable on the internal membranes of MIICs nor on exosomes. Because internal vesicles of multivesicular MIICs are thought to originate from inward budding of the limiting membrane, the differential distribution of membrane proteins on the internal and limiting membranes of MIICs has to be driven by active protein sorting.
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              Extracellular vesicles round off communication in the nervous system.

              Vivian Budnik, Catalina Ruiz-Cañada, Franz Wendler (2016)
              Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer. These extracellular vesicle functions add a previously unrecognized level of complexity to transcellular interactions within the nervous system.
              Article 0 comments Cited 331 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 04 April 2020
                Publication date Collection: April 2020
                Volume: 21
                Issue: 7
                Electronic Location Identifier: 2514
                Affiliations
                [1 ]Department of Medicine and Aging Sciences, University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy; simeone.pasquale@ 123456gmail.com (P.S.); giuseppina.bologna@ 123456hotmail.it (G.B.); laura.pierdomenico@ 123456unich.it (L.P.); mariateresa.guagnano@ 123456unich.it (M.T.G.); m.marchisio@ 123456unich.it (M.M.); s.miscia@ 123456unich.it (S.M.)
                [2 ]Center for Advanced Studies and Technology (C.A.S.T.), University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy; damiana.pieragostino@ 123456unich.it (D.P.); piero.delboccio@ 123456unich.it (P.D.B.); renato.mariani@ 123456unich.it (R.M.-C.)
                [3 ]Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy
                [4 ]Department of Pharmacy, University ‘‘G. d’Annunzio’’, Chieti-Pescara, 66100 Chieti, Italy
                [5 ]Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy; daniele.vergara@ 123456unisalento.it
                [6 ]Laboratory of Clinical Proteomics, “Giovanni Paolo II” Hospital, 73100 ASL-Lecce, Italy
                Author notes
                [* ]Correspondence: p.lanuti@ 123456unich.it ; Tel.: +39-0871-541392
                Author information
                https://orcid.org/0000-0003-4430-480X
                https://orcid.org/0000-0001-7225-0891
                https://orcid.org/0000-0002-2396-7674
                https://orcid.org/0000-0002-4440-1848
                Article
                Publisher ID: ijms-21-02514
                DOI: 10.3390/ijms21072514
                PMC ID: 7178048
                PubMed ID: 32260425
                SO-VID: 128c0052-fd1a-4070-a975-255873e4f8b2
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 18 February 2020
                Date accepted : 27 March 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: extracellular vesicles,biomarkers,liquid biopsy,biological barriers
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: extracellular vesicles, biomarkers, liquid biopsy, biological barriers

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