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Extracellular Vesicles in Cancer Development, Diagnostics, and Therapy
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Extracellular Vesicles in Cancer Development, Diagnostics, and Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 11568

Special Issue Editor

Prof. Dr. Maxim V. Berezovski

E-Mail Website
Guest Editor
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Interests: glioblastoma; lung cancer; molecular diagnostics; circulating tumor cells; tumor-derived exosomes; aptamers; proteomics; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Extracellular vesicles (EVs) deliver biomolecules from cells throughout the body, to individual cells, tissues, and whole organs. EVs can participate in a wide range of biological functions, such as eliminating unwanted materials, transfer of functional proteins and RNA, molecular recycling, signaling to the recipient cell via cell surface or endosomal receptors, and creation of a metastatic niche. Their cargo, including lipids, proteins, RNA, and DNA, provides a cell-specific signature of the cell of origin and reveals important insights about cancer transformation, tumor growth, and dissemination. As such, there is increasing excitement about their potential use as diagnostic and prognostic biomarkers and delivery tools for therapeutic purposes.

This Special Issue is aimed at summarizing both analytical developments and clinical evidence exploring the role of EVs in cancer development, diagnostic applications, and novel therapeutic approaches, to facilitate translational research and accelerate medical impacts in oncology.

Special Issue Highlights:

  • EV isolation, characterization, and normalization 
  • Tools for analysis of RNAseq and DNAseq data in EVs 
  • EVs and cancer detection
  • EVs and cancer therapy
  • EVs and viruses 
  • Novel technological developments

Prof. Dr. Maxim V. Berezovski
Guest Editor

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 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
  • exosomes
  • microvesicles
  • apoptotic bodies
  • oncosomes
  • ectosomes
  • cancer-derived extracellular vesicles
  • tumor-derived extracellular vesicles
  • biomarkers
  • cancer detection
  • therapy
  • theranostics

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Published Papers (4 papers)

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Research

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21 pages, 3411 KiB  
Article
MMP-9 as Prognostic Marker for Brain Tumours: A Comparative Study on Serum-Derived Small Extracellular Vesicles
by Gabriella Dobra, Edina Gyukity-Sebestyén, Mátyás Bukva, Mária Harmati, Valentina Nagy, Zoltán Szabó, Tibor Pankotai, Álmos Klekner and Krisztina Buzás
Cancers 2023, 15(3), 712; https://doi.org/10.3390/cancers15030712 - 24 Jan 2023
Cited by 13 | Viewed by 3559
Abstract
Matrix metalloproteinase-9 (MMP-9) degrades the extracellular matrix, contributes to tumour cell invasion and metastasis, and its elevated level in brain tumour tissues indicates poor prognosis. High-risk tissue biopsy can be replaced by liquid biopsy; however, the blood–brain barrier (BBB) prevents tumour-associated components from [...] Read more.
Matrix metalloproteinase-9 (MMP-9) degrades the extracellular matrix, contributes to tumour cell invasion and metastasis, and its elevated level in brain tumour tissues indicates poor prognosis. High-risk tissue biopsy can be replaced by liquid biopsy; however, the blood–brain barrier (BBB) prevents tumour-associated components from entering the peripheral blood, making the development of blood-based biomarkers challenging. Therefore, we examined the MMP-9 content of small extracellular vesicles (sEVs)—which can cross the BBB and are stable in body fluids—to characterise tumours with different invasion capacity. From four patient groups (glioblastoma multiforme, brain metastases of lung cancer, meningioma, and lumbar disc herniation as controls), 222 serum-derived sEV samples were evaluated. After isolating and characterising sEVs, their MMP-9 content was measured by ELISA and assessed statistically (correlation, paired t-test, Welch’s test, ANOVA, ROC). We found that the MMP-9 content of sEVs is independent of gender and age, but is affected by surgical intervention, treatment, and recurrence. We found a relation between low MMP-9 level in sEVs (<28 ppm) and improved survival (8-month advantage) of glioblastoma patients, and MMP-9 levels showed a positive correlation with aggressiveness. These findings suggest that vesicular MMP-9 level might be a useful prognostic marker for brain tumours. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Cancer Development, Diagnostics, and Therapy)
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17 pages, 3222 KiB  
Article
Isolation and Characterization of Extracellular Vesicles from Gastric Juice
by Gleb O. Skryabin, Svetlana V. Vinokurova, Sergey A. Galetsky, Danila S. Elkin, Alexey M. Senkovenko, Darya A. Denisova, Andrey V. Komelkov, Ivan S. Stilidi, Ivan N. Peregorodiev, Olga A. Malikhova, Oiatiddin T. Imaraliev, Adel D. Enikeev and Elena M. Tchevkina
Cancers 2022, 14(14), 3314; https://doi.org/10.3390/cancers14143314 - 7 Jul 2022
Cited by 7 | Viewed by 2475
Abstract
EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly [...] Read more.
EVs are involved in local and distant intercellular communication and play a vital role in cancer development. Since EVs have been found in almost all body fluids, there are currently active attempts for their application in liquid diagnostics. Blood is the most commonly used source of EVs for the screening of cancer markers, although the percentage of tumor-derived EVs in the blood is extremely low. In contrast, GJ, as a local biofluid, is expected to be enriched with GC-associated EVs. However, EVs from GJ have never been applied for the screening and are underinvestigated overall. Here we show that EVs can be isolated from GJ by ultracentrifugation. TEM analysis showed high heterogeneity of GJ-derived EVs, including those with exosome-like size and morphology. In addition to morphological diversity, EVs from individual GJ samples differed in the composition of exosomal markers. We also show the presence of stomatin within GJ-derived EVs for the first time. The first conducted comparison of miRNA content in EVs from GC patients and healthy donors performed using a pilot sampling revealed the significant differences in several miRNAs (-135b-3p, -199a-3p, -451a). These results demonstrate the feasibility of the application of GJ-derived EVs for screening for miRNA GC markers. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Cancer Development, Diagnostics, and Therapy)
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18 pages, 2455 KiB  
Article
Defining Optimal Conditions for Tumor Extracellular Vesicle DNA Extraction for Mutation Profiling
by Julia Elzanowska, Laura Berrocal, Beatriz García-Peláez, Marta Vives-Usano, Beatriz Passos Sebo, Joana Maia, Silvia Batista, Jaakko Teppo, Markku Varjosalo, Maria Carolina Strano Moraes, Miguel Ángel Molina-Vila and Bruno Costa-Silva
Cancers 2022, 14(13), 3258; https://doi.org/10.3390/cancers14133258 - 2 Jul 2022
Cited by 3 | Viewed by 2862
Abstract
(1) Background: Extracellular vesicles (EVs) have emerged as crucial players in the communication between cells in both physiological and pathological scenarios. The functions of EVs are strongly determined by their molecular content, which includes all bioactive molecules, such as proteins, lipids, RNA, and, [...] Read more.
(1) Background: Extracellular vesicles (EVs) have emerged as crucial players in the communication between cells in both physiological and pathological scenarios. The functions of EVs are strongly determined by their molecular content, which includes all bioactive molecules, such as proteins, lipids, RNA, and, as more recently described, double-stranded DNA. It has been shown that in oncological settings DNA associated with EVs (EV-DNA) is representative of the genome of parental cells and that it reflects the mutational status of the tumor, gaining much attention as a promising source of biomarker mutant DNA. However, one of the challenges in studies of EV-DNA is the lack of standardization of protocols for the DNA extraction from EVs, as well as ways to assess quality control, which hinders its future implementation in clinics. (2) Methods: We performed a comprehensive comparison of commonly used approaches for EV-DNA extraction by assessing DNA quantity, quality, and suitability for downstream analyses. (3) Results: We here established strategic points to consider for EV-DNA preparation for mutational analyses, including qPCR and NGS. (4) Conclusions: We put in place a workflow that can be applied for the detection of clinically relevant mutations in the EV-DNA of cancer patients. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Cancer Development, Diagnostics, and Therapy)
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Review

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21 pages, 2218 KiB  
Review
Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression
by Enea Ferlizza, Donatella Romaniello, Francesco Borrelli, Federica Pagano, Cinzia Girone, Valerio Gelfo, Rikke Sofie Kuhre, Alessandra Morselli, Martina Mazzeschi, Michela Sgarzi, Daria Maria Filippini, Gabriele D’Uva and Mattia Lauriola
Cancers 2023, 15(11), 2970; https://doi.org/10.3390/cancers15112970 - 30 May 2023
Cited by 4 | Viewed by 1994
Abstract
Extracellular vesicles (EVs) are of great interest to study the cellular mechanisms of cancer development and to diagnose and monitor cancer progression. EVs are a highly heterogeneous population of cell derived particles, which include microvesicles (MVs) and exosomes (EXOs). EVs deliver intercellular messages [...] Read more.
Extracellular vesicles (EVs) are of great interest to study the cellular mechanisms of cancer development and to diagnose and monitor cancer progression. EVs are a highly heterogeneous population of cell derived particles, which include microvesicles (MVs) and exosomes (EXOs). EVs deliver intercellular messages transferring proteins, lipids, nucleic acids, and metabolites with implications for tumour progression, invasiveness, and metastasis. Epidermal Growth Factor Receptor (EGFR) is a major driver of cancer. Tumour cells with activated EGFR could produce EVs disseminating EGFR itself or its ligands. This review provides an overview of EVs (mainly EXOs and MVs) and their cargo, with a subsequent focus on their production and effects related to EGFR activation. In particular, in vitro studies performed in EGFR-dependent solid tumours and/or cell cultures will be explored, thus shedding light on the interplay between EGFR and EVs production in promoting cancer progression, metastases, and resistance to therapies. Finally, an overview of liquid biopsy approaches involving EGFR and EVs in the blood/plasma of EGFR-dependent tumour patients will also be discussed to evaluate their possible application as candidate biomarkers. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Cancer Development, Diagnostics, and Therapy)
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