The role and application of small extracellular vesicles in gastric cancer

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Abstract

Gastric cancer (GC) is a common tumour that affects humans worldwide, is highly malignant and has a poor prognosis. Small extracellular vesicles (sEVs), especially exosomes, are nanoscale vesicles released by various cells that deliver bioactive molecules to recipient cells, affecting their biological characteristics, changing the tumour microenvironment and producing long-distance effects. In recent years, many studies have clarified the mechanisms by which sEVs function with regard to the initiation, progression, angiogenesis, metastasis and chemoresistance of GC. These molecules can function as mediators of cell-cell communication in the tumour microenvironment and might affect the efficacy of immunotherapy. Due to their unique physiochemical characteristics, sEVs show potential as effective antitumour vaccines as well as drug carriers. In this review, we summarize the roles of sEVs in GC and highlight the clinical application prospects in the future.

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Most cited references 174

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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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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

Suzy Torti, Donna D. Zhang, K.A. Woerpel … (2019)

Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels. Emerging evidence suggests that ferroptosis represents an ancient vulnerability caused by the incorporation of polyunsaturated fatty acids into cellular membranes, and cells have developed complex systems that exploit and defend against this vulnerability in different contexts. The sensitivity to ferroptosis is tightly linked to numerous biological processes, including amino acid, iron, and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH, and coenzyme Q10. Ferroptosis has been implicated in the pathological cell death associated with degenerative diseases (i.e., Alzheimer's, Huntington's, and Parkinson's diseases), carcinogenesis, stroke, intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration in mammals and is also implicated in heat stress in plants. Ferroptosis may also have a tumor-suppressor function that could be harnessed for cancer therapy. This Primer reviews the mechanisms underlying ferroptosis, highlights connections to other areas of biology and medicine, and recommends tools and guidelines for studying this emerging form of regulated cell death.

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Tumour exosome integrins determine organotropic metastasis

Ayuko Hoshino, Bruno Costa-Silva, Tang-Long Shen … (2015)

Ever since Stephen Paget’s 1889 hypothesis, metastatic organotropism has remained one of cancer’s greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver- and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins α6β4 and α6β1 were associated with lung metastasis, while exosomal integrin αvβ5 was linked to liver metastasis. Targeting the integrins α6β4 and αvβ5 decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

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Author and article information

Contributors

Liang Shang:

ORCID: https://orcid.org/0000-0002-9542-7650

docshang@163.com

Leping Li:

ORCID: http://orcid.org/0000-0003-2329-6791

lileping@sdu.edu.cn , lileping@medmail.com.cn

Journal

Journal ID (nlm-ta): Mol Cancer

Journal ID (iso-abbrev): Mol Cancer

Title: Molecular Cancer

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-4598

Publication date (Electronic): 29 April 2021

Publication date PMC-release: 29 April 2021

Publication date Collection: 2021

Volume: 20

Electronic Location Identifier: 71

Affiliations

[1 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, , Shandong University, ; Jinan, 250021 Shandong China

[2 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, Department of Clinical Medicine, Cheeloo College of Medicine, , Shandong University, ; Jinan, 250021 Shandong China

[3 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, , Shandong University, ; Jinan, 250021 Shandong China

[4 ]GRID grid.460018.b, ISNI 0000 0004 1769 9639, Department of Gastroenterological Surgery, , Shandong Provincial Hospital Affiliated to Shandong First Medical University, ; Jinan, 250021 Shandong China

[5 ]GRID grid.460018.b, ISNI 0000 0004 1769 9639, Department of Digestive Tumor Translational Medicine, Engineering Laboratory of Shandong Province, , Shandong Provincial Hospital, ; Jinan, 250021 Shandong China

Author information

Hao Wu https://orcid.org/0000-0001-9222-2521

Liang Shang https://orcid.org/0000-0002-9542-7650

Leping Li http://orcid.org/0000-0003-2329-6791

Article

Publisher ID: 1365

DOI: 10.1186/s12943-021-01365-z

PMC ID: 8081769

PubMed ID: 33926452

SO-VID: 0a701a7d-af1b-4363-a18f-37f703cc0371

License:

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 : 11 January 2021

Date accepted : 19 April 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100014103, Key Technology Research and Development Program of Shandong;

Award ID: 2019JZZY010104

Award ID: 2019GSF108146

Award Recipient : Liang Shang Leping Li

Funded by: Special Foundation for Taishan Scholars Program of Shandong Province

Award ID: ts20190978

Award Recipient : Leping Li

Funded by: Academic promotion programme of Shandong First Medical University

Award ID: 2019QL021

Award Recipient : Leping Li

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: gastric cancer,small extracellular vesicles,exosomes,diagnosis,therapy,molecular mechanism

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: gastric cancer, small extracellular vesicles, exosomes, diagnosis, therapy, molecular mechanism

The role and application of small extracellular vesicles in gastric cancer

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Karger: Oncology

Most cited references 174

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

Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

Tumour exosome integrins determine organotropic metastasis

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