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Cancers
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Extracellular Vesicles (EVs) in Cancer Diagnostics and Therapy
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Extracellular Vesicles (EVs) in Cancer Diagnostics and Therapy

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

Deadline for manuscript submissions: 31 March 2025 | Viewed by 8515

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,

This Special Issue titled "Extracellular Vesicles in Cancer Diagnostics and Therapy" delves into the pivotal role of extracellular vesicles (EVs) within oncological research. Extracellular vesicles, encompassing entities such as exosomes and microvesicles, represent a class of cell-derived nanoscale particles. These vesicles are increasingly acknowledged for their significant roles in intercellular communication and their potential as biomarkers and therapeutic vectors in cancer. This compendium of research and review articles illuminates the molecular mechanisms through which EVs influence tumorigenesis, metastasis, and the tumor microenvironment. It also explores the advancements in EV-based technologies for early cancer detection, monitoring, and the delivery of targeted therapeutics, thus underscoring their transformative impact on cancer diagnostics and treatment modalities.

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

  • cancer-derived extracellular vesicles
  • tumor-derived extracellular vesicles
  • exosomes or small EVs
  • microvesicles or large EVs
  • apoptotic bodies
  • oncosomes
  • EV biomarkers
  • EV diagnostics and prognostics
  • EV therapy
  • EV isolation

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Published Papers (4 papers)

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Research

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21 pages, 2584 KiB  
Article
Extracellular Vesicle microRNAs as Possible Liquid Biopsy Markers in HNSCC—A Longitudinal, Monocentric Study
by Carla Apeltrath, Frank Simon, Armands Riders, Claudia Rudack and Maximilian Oberste
Cancers 2024, 16(22), 3793; https://doi.org/10.3390/cancers16223793 - 11 Nov 2024
Viewed by 574
Abstract
Background: Biomarkers for HNSCC are still lacking. Biomolecules obtained via liquid biopsy are being investigated for diagnosis, prognosis, and therapy monitoring, including extracellular vesicles (EVs) and EV-cargo, e.g., proteins, RNA, and microRNA. This study aims to understand localization-dependent EV-microRNA expression in blood sera, [...] Read more.
Background: Biomarkers for HNSCC are still lacking. Biomolecules obtained via liquid biopsy are being investigated for diagnosis, prognosis, and therapy monitoring, including extracellular vesicles (EVs) and EV-cargo, e.g., proteins, RNA, and microRNA. This study aims to understand localization-dependent EV-microRNA expression in blood sera, their dynamics over time (12 months FU), and insights into their potential in diagnostics and therapy monitoring. Methods: Via liquid biopsy, blood serum was taken from 50 patients with HNSCC and 16 controls. Extracellular vesicles were isolated from serum by precipitation, and the contained microRNA-21, -1246, -200c, -let-7a, -181a, and -26a were amplified by reverse transcription and determined with real-time PCR. Expression ratios (HNSCC to healthy controls) were collated with the patients’ clinical parameters. A second liquid biopsy was carried out avg. 12 months later in the tumor aftercare. A sub-analysis with the Oropharynx subsite was implemented. Results: EV-mir-21, -let-7a, and -181a were 2.5–3-fold higher expressed in HPV/p16+ than in HPV/p16- HNSCC. Different expressions of EV-mir-181a and -26a could be demonstrated depending on the therapy modality. Conclusions: EV-microRNA could be a promising biomarker in the diagnosis and therapy monitoring of HNSCC. A systematic comparison of EV- and tissue microRNA expression in different HNSCC-subsites is needed. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Cancer Diagnostics and Therapy)
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16 pages, 2267 KiB  
Article
New Advances in the Study of CMTM6, a Focus on Its Novel Non-Canonical Cellular Locations, and Functions beyond Its Role as a PD-L1 Stabilizer
by Pedro Ivan Urciaga-Gutierrez, Ramon Antonio Franco-Topete, Blanca Estela Bastidas-Ramirez, Fabiola Solorzano-Ibarra, Jose Manuel Rojas-Diaz, Nadia Tatiana Garcia-Barrientos, Ksenia Klimov-Kravtchenko, Martha Cecilia Tellez-Bañuelos, Pablo Cesar Ortiz-Lazareno, Oscar Peralta-Zaragoza, Angelica Meneses-Acosta, Alan Guillermo Alejandre-Gonzalez, Miriam Ruth Bueno-Topete, Jesse Haramati and Susana del Toro-Arreola
Cancers 2024, 16(18), 3126; https://doi.org/10.3390/cancers16183126 - 11 Sep 2024
Viewed by 1092
Abstract
CMTM6 is a membrane protein that acts as a regulator of PD-L1, maintaining its expression on the cell surface, and can prevent its lysosome-mediated degradation. It is unknown if CMTM6 is present in the plasma of patients with cervical cancer, and if it [...] Read more.
CMTM6 is a membrane protein that acts as a regulator of PD-L1, maintaining its expression on the cell surface, and can prevent its lysosome-mediated degradation. It is unknown if CMTM6 is present in the plasma of patients with cervical cancer, and if it has non-canonical subcellular localizations in cell lines derived from cervical cancer. Our objective was to determine whether CMTM6 is found in plasma derived from cervical cancer patients and its subcellular localization in cell lines. Patient plasma was separated into exosome-enriched, exosome-free, and total plasma fractions. The levels of CMTM6 in each fraction were determined using ELISA and Western blot. Finally, for the cellular model, HeLa, SiHa, CaSki, and HaCaT were used; the subcellular locations of CMTM6 were determined using immunofluorescence and flow cytometry. Soluble CMTM6 was found to be elevated in plasma from patients with cervical cancer, with a nearly three-fold increase in patients (966.27 pg/mL in patients vs. 363.54 pg/mL in controls). CMTM6 was preferentially, but not exclusively, found in the exosome-enriched plasma fraction, and was positively correlated with exosomal PD-L1; CMTM6 was identified in the membrane, intracellular compartments, and culture supernatant of the cell lines. These results highlight that CMTM6, in its various presentations, may play an important role in the biology of tumor cells and in immune system evasion. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Cancer Diagnostics and Therapy)
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20 pages, 3015 KiB  
Article
Surface Proteome of Extracellular Vesicles and Correlation Analysis Reveal Breast Cancer Biomarkers
by Nico Hüttmann, Yingxi Li, Suttinee Poolsup, Emil Zaripov, Rochelle D’Mello, Vanessa Susevski, Zoran Minic and Maxim V. Berezovski
Cancers 2024, 16(3), 520; https://doi.org/10.3390/cancers16030520 - 25 Jan 2024
Viewed by 3037
Abstract
Breast cancer (BC) is the second most frequently diagnosed cancer and accounts for approximately 25% of new cancer cases in Canadian women. Using biomarkers as a less-invasive BC diagnostic method is currently under investigation but is not ready for practical application in clinical [...] Read more.
Breast cancer (BC) is the second most frequently diagnosed cancer and accounts for approximately 25% of new cancer cases in Canadian women. Using biomarkers as a less-invasive BC diagnostic method is currently under investigation but is not ready for practical application in clinical settings. During the last decade, extracellular vesicles (EVs) have emerged as a promising source of biomarkers because they contain cancer-derived proteins, RNAs, and metabolites. In this study, EV proteins from small EVs (sEVs) and medium EVs (mEVs) were isolated from BC MDA-MB-231 and MCF7 and non-cancerous breast epithelial MCF10A cell lines and then analyzed by two approaches: global proteomic analysis and enrichment of EV surface proteins by Sulfo-NHS-SS-Biotin labeling. From the first approach, proteomic profiling identified 2459 proteins, which were subjected to comparative analysis and correlation network analysis. Twelve potential biomarker proteins were identified based on cell line-specific expression and filtered by their predicted co-localization with known EV marker proteins, CD63, CD9, and CD81. This approach resulted in the identification of 11 proteins, four of which were further investigated by Western blot analysis. The presence of transmembrane serine protease matriptase (ST14), claudin-3 (CLDN3), and integrin alpha-7 (ITGA7) in each cell line was validated by Western blot, revealing that ST14 and CLDN3 may be further explored as potential EV biomarkers for BC. The surface labeling approach enriched proteins that were not identified using the first approach. Ten potential BC biomarkers (Glutathione S-transferase P1 (GSTP1), Elongation factor 2 (EEF2), DEAD/H box RNA helicase (DDX10), progesterone receptor (PGR), Ras-related C3 botulinum toxin substrate 2 (RAC2), Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), Aconitase 2 (ACO2), UTP20 small subunit processome component (UTP20), NEDD4 binding protein 2 (N4BP2), Programmed cell death 6 (PDCD6)) were selected from surface proteins commonly identified from MDA-MB-231 and MCF7, but not identified in MCF10A EVs. In total, 846 surface proteins were identified from the second approach, of which 11 were already known as BC markers. This study supports the proposition that Evs are a rich source of known and novel biomarkers that may be used for non-invasive detection of BC. Furthermore, the presented datasets could be further explored for the identification of potential biomarkers in BC. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Cancer Diagnostics and Therapy)
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Review

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18 pages, 1146 KiB  
Review
Advances in 3D Culture Models to Study Exosomes in Triple-Negative Breast Cancer
by Neelum Aziz Yousafzai, Lamyae El Khalki, Wei Wang, Justin Szpendyk and Khalid Sossey-Alaoui
Cancers 2024, 16(5), 883; https://doi.org/10.3390/cancers16050883 - 22 Feb 2024
Cited by 3 | Viewed by 3378
Abstract
Breast cancer, a leading cause of cancer-related deaths globally, exhibits distinct subtypes with varying pathological, genetic, and clinical characteristics. Despite advancements in breast cancer treatments, its histological and molecular heterogeneity pose a significant clinical challenge. Triple-negative breast cancer (TNBC), a highly aggressive subtype [...] Read more.
Breast cancer, a leading cause of cancer-related deaths globally, exhibits distinct subtypes with varying pathological, genetic, and clinical characteristics. Despite advancements in breast cancer treatments, its histological and molecular heterogeneity pose a significant clinical challenge. Triple-negative breast cancer (TNBC), a highly aggressive subtype lacking targeted therapeutics, adds to the complexity of breast cancer treatment. Recent years have witnessed the development of advanced 3D culture technologies, such as organoids and spheroids, providing more representative models of healthy human tissue and various malignancies. These structures, resembling organs in structure and function, are generated from stem cells or organ-specific progenitor cells via self-organizing processes. Notably, 3D culture systems bridge the gap between 2D cultures and in vivo studies, offering a more accurate representation of in vivo tumors’ characteristics. Exosomes, small nano-sized molecules secreted by breast cancer and stromal/cancer-associated fibroblast cells, have garnered significant attention. They play a crucial role in cell-to-cell communication, influencing tumor progression, invasion, and metastasis. The 3D culture environment enhances exosome efficiency compared to traditional 2D cultures, impacting the transfer of specific cargoes and therapeutic effects. Furthermore, 3D exosomes have shown promise in improving therapeutic outcomes, acting as potential vehicles for cancer treatment administration. Studies have demonstrated their role in pro-angiogenesis and their innate therapeutic potential in mimicking cellular therapies without side effects. The 3D exosome model holds potential for addressing challenges associated with drug resistance, offering insights into the mechanisms underlying multidrug resistance and serving as a platform for drug screening. This review seeks to emphasize the crucial role of 3D culture systems in studying breast cancer, especially in understanding the involvement of exosomes in cancer pathology. Full article
(This article belongs to the Special Issue Extracellular Vesicles (EVs) in Cancer Diagnostics and Therapy)
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