Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

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Abstract

The current diagnosis and treatment of sarcoma continue to show limited timeliness and efficacy. In order to enable the early detection and management of sarcoma, increasing attentions have been given to the tumor microenvironment (TME). TME is a dynamic network composed of multiple cells, extracellular matrix, vasculature, and exosomes. Exosomes are nano-sized extracellular vesicles derived from various cells in the TME. The major function of exosomes is to promote cancer progress and metastasis through mediating bidirectional cellular communications between sarcoma cells and TME cells. Due to the content specificity, cell tropism, and bioavailability, exosomes have been regarded as promising diagnostic and prognostic biomarkers, and therapeutic vehicles for sarcoma. This review summarizes recent studies on the roles of exosomes in TME of sarcoma, and explores the emerging clinical applications.

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Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Clotilde Théry, Kenneth W Witwer, Elena Aikawa … (2019)

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

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Rab27a and Rab27b control different steps of the exosome secretion pathway.

Matias Ostrowski, Nuno Carmo, Sophie Krumeich … (2010)

Exosomes are secreted membrane vesicles that share structural and biochemical characteristics with intraluminal vesicles of multivesicular endosomes (MVEs). Exosomes could be involved in intercellular communication and in the pathogenesis of infectious and degenerative diseases. The molecular mechanisms of exosome biogenesis and secretion are, however, poorly understood. Using an RNA interference (RNAi) screen, we identified five Rab GTPases that promote exosome secretion in HeLa cells. Among these, Rab27a and Rab27b were found to function in MVE docking at the plasma membrane. The size of MVEs was strongly increased by Rab27a silencing, whereas MVEs were redistributed towards the perinuclear region upon Rab27b silencing. Thus, the two Rab27 isoforms have different roles in the exosomal pathway. In addition, silencing two known Rab27 effectors, Slp4 (also known as SYTL4, synaptotagmin-like 4) and Slac2b (also known as EXPH5, exophilin 5), inhibited exosome secretion and phenocopied silencing of Rab27a and Rab27b, respectively. Our results therefore strengthen the link between MVEs and exosomes, and introduce ways of manipulating exosome secretion in vivo.

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Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance

Ladan Mashouri, Hassan Yousefi, Amir Reza Aref … (2019)

Tumor-derived exosomes (TDEs) participate in formation and progression of different cancer processes, including tumor microenvironment (TME) remodeling, angiogenesis, invasion, metastasis and drug-resistance. Exosomes initiate or suppress various signaling pathways in the recipient cells via transmitting heterogeneous cargoes. In this review we discuss exosome biogenesis, exosome mediated metastasis and chemoresistance. Furthermore, tumor derived exosomes role in tumor microenvironment remodeling, and angiogenesis is reviewed. Also, exosome induction of epithelial mesenchymal transition (EMT) is highlighted. More importantly, we discuss extensively how exosomes regulate drug resistance in several cancers. Thus, understanding exosome biogenesis, their contents and the molecular mechanisms and signaling pathways that are responsible for metastasis and drug-resistance mediated by TDEs may help to devise novel therapeutic approaches for cancer progression particularly to overcome therapy-resistance and preventing metastasis as major factors of cancer mortality. Electronic supplementary material The online version of this article (10.1186/s12943-019-0991-5) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Zhenfeng Duan: zxd221@med.miami.edu

Li Min: minli1204@scu.edu.cn

Journal

Journal ID (nlm-ta): J Nanobiotechnology

Journal ID (iso-abbrev): J Nanobiotechnology

Title: Journal of Nanobiotechnology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-3155

Publication date (Electronic): 5 September 2022

Publication date PMC-release: 5 September 2022

Publication date Collection: 2022

Volume: 20

Electronic Location Identifier: 403

Affiliations

[1 ]GRID grid.412901.f, ISNI 0000 0004 1770 1022, Orthopedic Research Institute, Department of Orthopedics, , West China Hospital, Sichuan University, ; Chengdu, China

[2 ]GRID grid.13291.38, ISNI 0000 0001 0807 1581, West China Hospital, West China School of Medicine, , Sichuan University, ; Chengdu, China

[3 ]GRID grid.419791.3, ISNI 0000 0000 9902 6374, Sarcoma Biology Laboratory, Department of Orthopaedics, , Sylvester Comprehensive Cancer Center, and the University of Miami Miller School of Medicine, ; Miami, FL 33136 USA

Article

Publisher ID: 1609

DOI: 10.1186/s12951-022-01609-0

PMC ID: 9446729

PubMed ID: 36064358

SO-VID: 01d5133a-1996-49bb-8eb4-e42400270ba3

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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

Date received : 21 May 2022

Date accepted : 23 August 2022

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ScienceOpen disciplines: Biotechnology

Keywords: exosomes,tumor microenvironment,sarcoma,communication,clinical application

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ScienceOpen disciplines: Biotechnology

Keywords: exosomes, tumor microenvironment, sarcoma, communication, clinical application

Exosomes in the tumor microenvironment of sarcoma: from biological functions to clinical applications

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Most cited references 109

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Rab27a and Rab27b control different steps of the exosome secretion pathway.

Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance

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