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      The role of extracellular vesicles in cholangiocarcinoma

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          Abstract

          Cholangiocarcinoma (CCA) is a rare tumor that arises from cholangiocytes, the epithelial cells of the bile duct. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis and high recurrence rate. Due to the lack of specific biomarkers, it is difficult to diagnose CCA early and evaluate prognosis. Extracellular vesicles (EVs), which include apoptotic bodies, microvesicles and exosomes, have emerged as having important roles in cell-to-cell communication in both normal physiology and pathological conditions. Some research has found that EVs play a crucial role in the occurrence and development of CCA. EVs can carry specific molecular substances such as nucleic acids and proteins, which have potential for the diagnosis and therapy of CCA. This article reviews the current knowledge on the role of EVs in CCA. We highlight EVs and their functions in the physiology and pathophysiology of CCA, and discuss their therapeutic potential and their role as biomarkers.

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          Most cited references120

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          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            Shedding light on the cell biology of extracellular vesicles

            Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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              Molecular mechanisms of epithelial-mesenchymal transition.

              The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.
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                Author and article information

                Contributors
                ldyy_linyy@lzu.edu.cn
                mengwb@lzu.edu.cn
                Journal
                Cancer Cell Int
                Cancer Cell Int
                Cancer Cell International
                BioMed Central (London )
                1475-2867
                4 September 2020
                4 September 2020
                2020
                : 20
                : 435
                Affiliations
                [1 ]GRID grid.32566.34, ISNI 0000 0000 8571 0482, The First Clinical Medical College, , Lanzhou University, ; Lanzhou, 730000 China
                [2 ]GRID grid.412643.6, Department of Special Minimally Invasive Surgery, , The First hospital of Lanzhou University, ; Lanzhou, 730000 China
                [3 ]GRID grid.412643.6, Division of Scientific Research and Development Planning, , The First Hospital of Lanzhou University, ; Lanzhou, 730000 China
                [4 ]GRID grid.32566.34, ISNI 0000 0000 8571 0482, Institute of Genetics, School of Basic Medical Sciences, , Lanzhou University, ; 730000 Lanzhou, China
                [5 ]Gansu Province Institute of Hepatopancreatobiliary, 730000 Lanzhou, China
                [6 ]Gansu Province Key Laboratory Biotherapy and Regenerative Medicine, 730000 Lanzhou, China
                [7 ]GRID grid.412643.6, The Second Department of General Surgery, , The First Hospital of Lanzhou University, ; 730000 Lanzhou, China
                Author information
                http://orcid.org/0000-0002-9355-0225
                Article
                1526
                10.1186/s12935-020-01526-y
                7709354
                9b2a33ca-2b5e-4f9c-8a1c-146b144c14f7
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 June 2020
                : 29 August 2020
                Funding
                Funded by: National Natural Science Foundation
                Award ID: 81872036
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100007764, Lanzhou Science and Technology Bureau;
                Award ID: 2019-4-43
                Award Recipient :
                Funded by: Science and Technology Project of Chengguan District of Lanzhou City
                Award ID: 2019JSCX0092
                Award ID: 2019RCCX0038
                Award Recipient :
                Funded by: Lanzhou talent innovation project
                Award ID: 2018-RC-13
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                cholangiocarcinoma,extracellular vesicles,exosomes,biomarkers,therapy
                Oncology & Radiotherapy
                cholangiocarcinoma, extracellular vesicles, exosomes, biomarkers, therapy

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