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      The “sugar‐coated bullets” of cancer: Tumor‐derived exosome surface glycosylation from basic knowledge to applications

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          Abstract

          Scientific interest in exosomes has exploded in recent decades. In 1990 only three articles were published on exosomes, while over 1,700 have already been published half‐way into 2020. 1 While researchers have shown much interest in exosomes since being discovered in 1981, an appreciation of the potential role of glycans in exosome structure and function has emerged only recently. Glycosylation is one of the most common post‐translational modification, which functions in many physiological and pathological aspects of cellular function. Many components of exosomes are heavily glycosylated including proteins, lipids, among others. Thus, glycosylation undoubtedly has a great impact on exosome biosynthesis and function. Despite the importance of glycosylation in exosomes and the recent recognition of them as biomarkers for not only malignancies but also other system dysfunction and disease, the characterization of exosome glycans remains understudied. In this review, we discuss glycosylation patterns of exosomes derived from various tissues, their biological features, and potential for various clinical applications. We highlight state‐of‐the‐art knowledge about the fine structure of exosomes, which will allow researchers to reconstruct them by surface modification. These efforts will likely lead to novel disease‐related biomarker discovery, purification tagging, and targeted drug transfer for clinical applications in the future.

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          Most cited references66

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          Glycosylation in cancer: mechanisms and clinical implications.

          Despite recent progress in understanding the cancer genome, there is still a relative delay in understanding the full aspects of the glycome and glycoproteome of cancer. Glycobiology has been instrumental in relevant discoveries in various biological and medical fields, and has contributed to the deciphering of several human diseases. Glycans are involved in fundamental molecular and cell biology processes occurring in cancer, such as cell signalling and communication, tumour cell dissociation and invasion, cell-matrix interactions, tumour angiogenesis, immune modulation and metastasis formation. The roles of glycans in cancer have been highlighted by the fact that alterations in glycosylation regulate the development and progression of cancer, serving as important biomarkers and providing a set of specific targets for therapeutic intervention. This Review discusses the role of glycans in fundamental mechanisms controlling cancer development and progression, and their applications in oncology.
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            Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis.

            Tumor-secreted extracellular vesicles (EVs) are critical mediators of intercellular communication between tumor cells and stromal cells in local and distant microenvironments. Accordingly, EVs play an essential role in both primary tumor growth and metastatic evolution. EVs orchestrate multiple systemic pathophysiological processes, such as coagulation, vascular leakiness, and reprogramming of stromal recipient cells to support pre-metastatic niche formation and subsequent metastasis. Clinically, EVs may be biomarkers and novel therapeutic targets for cancer progression, particularly for predicting and preventing future metastatic development.
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              Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor.

              The fate of the transferrin receptor during in vitro maturation of sheep reticulocytes has been followed using FITC- and 125I-labeled anti-transferrin-receptor antibodies. Vesicles containing peptides that comigrate with the transferrin receptor on polyacrylamide gels are released during incubation of sheep reticulocytes, tagged with anti-transferrin-receptor antibodies. Vesicle formation does not require the presence of the anti-transferrin-receptor antibodies. Using 125I-surface-labeled reticulocytes, it can be shown that the 125I-labeled material which is released is retained by an immunoaffinity column of the anti-transferrin-receptor antibody. Using reticulocytes tagged with 125I-labeled anti-transferrin-receptor antibodies to follow the formation of vesicles, it can be shown that at 0 degree C or in phosphate-buffered saline the rate of vesicle release is less than that at 37 degrees C in culture medium. There is selective externalization of the antibody-receptor complex since few other membrane proteins are found in the externalized vesicles. The anti-transferrin-receptor antibodies cause redistribution of the receptor into patches that do not appear to be required for vesicle formation.
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                Author and article information

                Contributors
                zhoushumin_zw@126.com
                terrenceyuan@gmail.com
                Journal
                Clin Transl Med
                Clin Transl Med
                10.1002/(ISSN)2001-1326
                CTM2
                Clinical and Translational Medicine
                John Wiley and Sons Inc. (Hoboken )
                2001-1326
                13 October 2020
                October 2020
                : 10
                : 6 ( doiID: 10.1002/ctm2.v10.6 )
                : e204
                Affiliations
                [ 1 ] Department of Orthopaedic Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai P. R. China
                [ 2 ] Institute of Microsurgery on Extremities Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai P. R. China
                Author notes
                [*] [* ] Correspondence

                Shumin Zhou, Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.

                Email: zhoushumin_zw@ 123456126.com

                Ting Yuan, Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, P. R. China.

                Email: terrenceyuan@ 123456gmail.com

                Author information
                https://orcid.org/0000-0001-9657-9771
                Article
                CTM2204
                10.1002/ctm2.204
                7551131
                33135347
                66597e2f-1564-4800-9e0f-ea453469d3bc
                © 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 July 2020
                : 29 August 2020
                : 28 September 2020
                Page count
                Figures: 7, Tables: 1, Pages: 13, Words: 6799
                Funding
                Funded by: Shanghai Jiaotong University medical industry
                Award ID: YG2017MS21
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.2 mode:remove_FC converted:13.10.2020

                Medicine
                biomarkers,exosomes,glycosylation,purification,targeting therapy
                Medicine
                biomarkers, exosomes, glycosylation, purification, targeting therapy

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