Biogenesis and Function of Extracellular Vesicles in Cancers

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 9921

Special Issue Editors

Department of Pediatric Hematology and Oncology, University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Interests: proteomics and genomics of extracellular vesicles; heterogeneity of extracellular vesicles; cell-to-cell communica-tion in cancer; tumor microenvironment; tumor progression
1. Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden
2. Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA
Interests: microRNA and proteomics of extracellular vesicles; pre-metastatic niche; microenvironment; extracellular-vesicle-based cell-to-cell communication in metastasis progression

Special Issue Information

Dear Colleagues,

Research on the function of small extracellular vesicles (EVs), including exosomes, has emerged as a field of great interest in cell and tumor biology. Based on their potential as biomarkers and mediators of cell-to-cell communication by horizontal transfer of active biomolecules, we aim to bring together investigators interested in understanding EV-based cell-to-cell communication in cancer. We believe that a detailed view of how tumor-derived EVs communicate with the microenvironment by delivering their biological cargo will lead to new directions in the field of cancer treatment.

Due to the exposure of the translational aspect of EVs, we believe that regulating how EVs are released is essential to understand how different classes of EVs mediate specific biological responses. In the tumor microenvironment, EVs released from tumor cells can act upon stromal cells or immune cells, for example, to prepare the niche for the future arrival of tumor cells in the process of metastasis. In addition, in cancer relapse, it is now noted that modulation of cells in the microenvironment niche via tumor EVs can favor the survival and expansion of tumor cells. This is just an example of the high translational relevance of EVs in tumor biology. 

The mechanism of tumor-derived EVs in communication with microenvironmental niches focuses on metastasis, relapse, and resistance to therapy.

This Special Issue will focus on the mechanism of biogenesis of tumor EVs loaded with the biological cargo, protein, lipids, and nucleic acids. Further, the current issue will cover physiological effects involved in EV-based cell-to-cell communication in tumor progressions such as angiogenesis, epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and immune escape.

Dr. Basant Kumar Thakur
Dr. Linda Bojmar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • extracellular vesicles and particles
  • proteomics and genomics
  • cancer
  • tumor microenvironment
  • cell-to-cell communication
  • metastasis

Published Papers (3 papers)

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Research

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23 pages, 38669 KiB  
Article
Efficient Small Extracellular Vesicles (EV) Isolation Method and Evaluation of EV-Associated DNA Role in Cell–Cell Communication in Cancer
by Venkatesh Kumar Chetty, Jamal Ghanam, Srishti Anchan, Katarina Reinhardt, Alexandra Brenzel, Márton Gelléri, Christoph Cremer, Elena Grueso-Navarro, Markus Schneider, Nils von Neuhoff, Dirk Reinhardt, Jadwiga Jablonska, Irina Nazarenko and Basant Kumar Thakur
Cancers 2022, 14(9), 2068; https://doi.org/10.3390/cancers14092068 - 20 Apr 2022
Cited by 6 | Viewed by 4763
Abstract
Small extracellular vesicles (sEVs) play essential roles in intercellular signaling both in normal and pathophysiological conditions. Comprehensive studies of dsDNA associated with sEVs are hampered by a lack of methods, allowing efficient separation of sEVs from free-circulating DNA and apoptotic bodies. In this [...] Read more.
Small extracellular vesicles (sEVs) play essential roles in intercellular signaling both in normal and pathophysiological conditions. Comprehensive studies of dsDNA associated with sEVs are hampered by a lack of methods, allowing efficient separation of sEVs from free-circulating DNA and apoptotic bodies. In this work, using controlled culture conditions, we enriched the reproducible separation of sEVs from free-circulated components by combining tangential flow filtration, size-exclusion chromatography, and ultrafiltration (TSU). EV-enriched fractions (F2 and F3) obtained using TSU also contained more dsDNA derived from the host genome and mitochondria, predominantly localized inside the vesicles. Three-dimensional reconstruction of high-resolution imaging showed that the recipient cell membrane barrier restricts a portion of EV-DNA. Simultaneously, the remaining EV-DNA overcomes it and enters the cytoplasm and nucleus. In the cytoplasm, EV-DNA associates with dsDNA-inflammatory sensors (cGAS/STING) and endosomal proteins (Rab5/Rab7). Relevant to cancer, we found that EV-DNA isolated from leukemia cell lines communicates with mesenchymal stromal cells (MSCs), a critical component in the BM microenvironment. Furthermore, we illustrated the arrangement of sEVs and EV-DNA at a single vesicle level using super-resolution microscopy. Altogether, employing TSU isolation, we demonstrated EV-DNA distribution and a tool to evaluate the exact EV-DNA role of cell–cell communication in cancer. Full article
(This article belongs to the Special Issue Biogenesis and Function of Extracellular Vesicles in Cancers)
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Review

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23 pages, 2693 KiB  
Review
From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research
by Nicolas Cheuk Hang Lau and Judy Wai Ping Yam
Cancers 2023, 15(7), 1992; https://doi.org/10.3390/cancers15071992 - 27 Mar 2023
Cited by 7 | Viewed by 2273
Abstract
Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which [...] Read more.
Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which may in turn impact delivery, uptake and cargo function in recipient cells. A mechanistic understanding of exosome biology is therefore crucial to investigating exosomal function in complex biological systems and to the development of novel therapeutic approaches. Here, we outline the steps in exosome biogenesis, including endosome formation, MVB formation, cargo sorting and extracellular release, as well as exosome absorption, including targeting, interaction with recipient cells and the fate of internalized exosomes. In addition to providing a framework of exosome dynamics, we summarize current evidence on major pathways and regulatory mechanisms. We also highlight the various mechanisms observed in cancer and point out directions to improve study design in exosome biology. Further research is needed to illuminate the relationship between exosome biogenesis and function, which will aid the development of translational applications. Full article
(This article belongs to the Special Issue Biogenesis and Function of Extracellular Vesicles in Cancers)
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29 pages, 3483 KiB  
Review
Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis
by Haijiao Jing, Xiaoming Wu, Mengqi Xiang, Chengyue Wang, Valerie A. Novakovic and Jialan Shi
Cancers 2023, 15(7), 1957; https://doi.org/10.3390/cancers15071957 - 24 Mar 2023
Cited by 3 | Viewed by 2290
Abstract
Tumor progression and cancer metastasis has been linked to the release of microparticles (MPs), which are shed upon cell activation or apoptosis and display parental cell antigens, phospholipids such as phosphatidylserine (PS), and nucleic acids on their external surfaces. In this review, we [...] Read more.
Tumor progression and cancer metastasis has been linked to the release of microparticles (MPs), which are shed upon cell activation or apoptosis and display parental cell antigens, phospholipids such as phosphatidylserine (PS), and nucleic acids on their external surfaces. In this review, we highlight the biogenesis of MPs as well as the pathophysiological processes of PS externalization and its involvement in coagulation activation. We review the available evidence, suggesting that coagulation factors (mainly tissue factor, thrombin, and fibrin) assist in multiple steps of tumor dissemination, including epithelial–mesenchymal transition, extracellular matrix remodeling, immune escape, and tumor angiogenesis to support the formation of the pre-metastatic niche. Platelets are not just bystander cells in circulation but are functional players in primary tumor growth and metastasis. Tumor-induced platelet aggregation protects circulating tumor cells (CTCs) from the blood flow shear forces and immune cell attack while also promoting the binding of CTCs to endothelial cells and extravasation, which activates tumor invasion and sustains metastasis. Finally, in terms of therapy, lactadherin can inhibit coagulation by competing effectively with coagulation factors for PS binding sites and may similarly delay tumor progression. Furthermore, we also investigate the therapeutic potential of coagulation factor inhibitors within the context of cancer treatment. The development of multiple therapies targeting platelet activation and platelet–tumor cell interactions may not only reduce the lethal consequences of thrombosis but also impede tumor growth and spread. Full article
(This article belongs to the Special Issue Biogenesis and Function of Extracellular Vesicles in Cancers)
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