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      Exosome derived from tumor-associated macrophages: biogenesis, functions, and therapeutic implications in human cancers

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          Abstract

          Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50–150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer. Recent studies have suggested that TAMs-derived exosomes play crucial roles in malignant cell proliferation, invasion, metastasis, angiogenesis, immune responses, drug resistance, and tumor metabolic reprogramming. TAMs-derived exosomes have the potential to be targeted for tumor therapy. In addition, the abnormal expression of non-coding RNAs and proteins in TAMs-derived exosomes is closely related to the clinicopathological features of patients with cancer, and these exosomes are expected to become new liquid biopsy markers for the early diagnosis, prognosis, and monitoring of tumors. In this review, we explored the role of TAMs-derived exosomes in tumorigenesis to provide new diagnostic biomarkers and therapeutic targets for cancer prevention.

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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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              Tumor metastasis: molecular insights and evolving paradigms.

              Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                meicheng@csu.edu.cn
                ouchunlin@csu.edu.cn
                Journal
                Biomark Res
                Biomark Res
                Biomarker Research
                BioMed Central (London )
                2050-7771
                19 November 2023
                19 November 2023
                2023
                : 11
                : 100
                Affiliations
                [1 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Pathology, Xiangya Hospital, , Central South University, ; Changsha, 410008 Hunan China
                [2 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Departments of Ultrasound Imaging, Xiangya Hospital, , Central South University, ; Changsha, 410008 Hunan China
                [3 ]Department of Blood Transfusion, Xiangya Hospital, Clinical Transfusion Research Center, Central South University, ( https://ror.org/00f1zfq44) Changsha, 410008 Hunan China
                [4 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, , Central South University, ; Changsha, China
                Article
                538
                10.1186/s40364-023-00538-w
                10658727
                37981718
                c36581c5-27e8-4e9f-8383-730a411c39c8
                © The Author(s) 2023

                Open Access This 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
                : 30 July 2023
                : 5 November 2023
                Funding
                Funded by: Natural Science Foundation of Hunan Province
                Award ID: 2022JJ40784
                Award ID: 2023JJ40975
                Award ID: 2021JJ41013
                Funded by: National Natural Science Foundation of China
                Award ID: 81903032
                Funded by: China Postdoctoral Science Foundation
                Award ID: 2020M672520
                Funded by: Outstanding Youth Foundation of Hunan Provincial Natural Science Foundation of China
                Award ID: 2022JJ20098
                Categories
                Review
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                © Yumed Inc. and BioMed Central Ltd., part of Springer Nature 2023

                tumor-associated macrophages,exosomes,tumor microenvironment,metabolic reprogramming,liquid biopsy,therapeutic target

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