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Advance in Exosomes in Tumors
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Advance in Exosomes in Tumors

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 8818

Special Issue Editor

Dr. Karin Ekström

E-Mail Website
Guest Editor
Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden
Interests: extracellular vesicles; exosomes; cancer; regenerative medicine

Special Issue Information

Dear Colleagues,

The involvement of extracellular vesicles (EVs) in cancer development as well as the potential use of EVs in cancer therapy and as biomarkers is gaining increased interest in the cancer and EV research field.

EVs, such as exosomes and microvesicles, are nano-sized membrane vesicles participating in inter-cellular communication. EVs are released from most cells and can also be isolated from tissue and body fluids including urine, blood, saliva, ascites, pleural effusions, cerebrospinal fluid, and nasal secretions. EVs are involved in normal physiology but have also been suggested to be involved in a wide range of diseases, including cancer. Accumulating data suggest that EVs play an important role in tumor growth and tumor metastases by facilitating cell proliferation, migration, angiogenesis, and immune modulation, as well as cell survival. Further knowledge of the role of EVs in these events is of importance to increase the understanding of cancer biology and for future treatments and early diagnosis.

This Special Issue on “Advances in Exosomes in Tumors” welcomes original and review articles focusing on all aspects of EVs in cancer biology, including tumor growth and metastases, biomarkers, novel detection methods, and therapy.

Dr. Karin Ekström
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 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • cancer
  • cancer therapy
  • biomarkers

Published Papers (5 papers)

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Research

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19 pages, 5242 KiB  
Article
Vesicular Release and Uptake of Circular LSD1-RNAs from Non-Cancer and Cancer Lung Cells
by Joelle Noriko Galang, Yefeng Shen, Ulrike Koitzsch, Xiaojie Yu, Hannah Eischeid-Scholz, Daniel Bachurski, Tilman T. Rau, Christina Neppl, Marco Herling, Bianca Bulimaga, Elena Vasyutina, Michal R. Schweiger, Reinhard Büttner, Margarete Odenthal and Maria M. Anokhina
Int. J. Mol. Sci. 2023, 24(18), 13981; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241813981 - 12 Sep 2023
Cited by 1 | Viewed by 944
Abstract
Lysine-specific demethylase 1 (LSD1) is highly expressed in many cancer types and strongly associated with cancer progression and metastasis. Circular RNAs (circRNAs) are produced by back-splicing and influence the interactive RNA network by microRNA and protein sponging. In the present study, we aimedto [...] Read more.
Lysine-specific demethylase 1 (LSD1) is highly expressed in many cancer types and strongly associated with cancer progression and metastasis. Circular RNAs (circRNAs) are produced by back-splicing and influence the interactive RNA network by microRNA and protein sponging. In the present study, we aimedto identify circRNAs that derive from the LSD1-encoding KDM1A gene, and to investigate their potential to be released and uptaken by lung cancer versus non-cancer epithelial cells. We identified four circLSD1-RNAs by RT-PCR with divergent primers, followed by sequencing. The expression level of circLSD1-RNAs was then studied by quantitative PCR on cellular and extracellular fractions of lung cancer (PC9) and non-cancer primary small airway epithelial (PSAE) cells. Moreover, we established the transgenic overexpression of circLSD1-RNAs. We show that circLSD1-RNAs are primarily located in the cytoplasm, but are packaged and released from lung cancer and non-cancer cells by extracellular vesicles (EVs) and ribonucleoprotein (RNP) complexes, respectively. Proteomics demonstrated a different protein pattern of EV fractions released from PC9 versus PSAE cells. Importantly, released circLSD1-RNAs were differently taken up by PSAE and PC9 cells. In conclusion, our findings provide primary evidence that circLSD1-RNAs participate in the intercellular communication of lung cancer cells with the tumor environment. Full article
(This article belongs to the Special Issue Advance in Exosomes in Tumors)
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13 pages, 2902 KiB  
Communication
Glycan Node Analysis Detects Varying Glycosaminoglycan Levels in Melanoma-Derived Extracellular Vesicles
by Jenifer Pendiuk Goncalves, Sierra A. Walker, Jesús S. Aguilar Díaz de león, Yubo Yang, Irina Davidovich, Sara Busatto, Jann Sarkaria, Yeshayahu Talmon, Chad R. Borges and Joy Wolfram
Int. J. Mol. Sci. 2023, 24(10), 8506; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24108506 - 09 May 2023
Cited by 6 | Viewed by 1547
Abstract
Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are [...] Read more.
Extracellular vesicles (EVs) play important roles in (patho)physiological processes by mediating cell communication. Although EVs contain glycans and glycosaminoglycans (GAGs), these biomolecules have been overlooked due to technical challenges in comprehensive glycome analysis coupled with EV isolation. Conventional mass spectrometry (MS)-based methods are restricted to the assessment of N-linked glycans. Therefore, methods to comprehensively analyze all glyco-polymer classes on EVs are urgently needed. In this study, tangential flow filtration-based EV isolation was coupled with glycan node analysis (GNA) as an innovative and robust approach to characterize most major glyco-polymer features of EVs. GNA is a molecularly bottom-up gas chromatography-MS technique that provides unique information that is unobtainable with conventional methods. The results indicate that GNA can identify EV-associated glyco-polymers that would remain undetected with conventional MS methods. Specifically, predictions based on GNA identified a GAG (hyaluronan) with varying abundance on EVs from two different melanoma cell lines. Enzyme-linked immunosorbent assays and enzymatic stripping protocols confirmed the differential abundance of EV-associated hyaluronan. These results lay the framework to explore GNA as a tool to assess major glycan classes on EVs, unveiling the EV glycocode and its biological functions. Full article
(This article belongs to the Special Issue Advance in Exosomes in Tumors)
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14 pages, 2743 KiB  
Article
Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma
by Hiroshi Maruoka, Tomohito Tanaka, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Misa Nunode, Atsushi Daimon, Shunsuke Miyamoto, Ruri Nishie, Shoko Ueda, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura and Masahide Ohmichi
Int. J. Mol. Sci. 2022, 23(24), 15715; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415715 - 11 Dec 2022
Cited by 2 | Viewed by 1478
Abstract
Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative [...] Read more.
Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC. Full article
(This article belongs to the Special Issue Advance in Exosomes in Tumors)
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Review

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19 pages, 1211 KiB  
Review
New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment
by Biying Yan and Yaxuan Liang
Int. J. Mol. Sci. 2022, 23(24), 15758; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415758 - 12 Dec 2022
Cited by 7 | Viewed by 2728
Abstract
Cancers are defined by genetic defects, which underlines the prospect of using gene therapy in patient care. During the past decade, CRISPR technology has rapidly evolved into a powerful gene editing tool with high fidelity and precision. However, one of the impediments slowing [...] Read more.
Cancers are defined by genetic defects, which underlines the prospect of using gene therapy in patient care. During the past decade, CRISPR technology has rapidly evolved into a powerful gene editing tool with high fidelity and precision. However, one of the impediments slowing down the clinical translation of CRISPR-based gene therapy concerns the lack of ideal delivery vectors. Extracellular vesicles (EVs) are nano-sized membrane sacs naturally released from nearly all types of cells. Although EVs are secreted for bio-information conveyance among cells or tissues, they have been recognized as superior vectors for drug or gene delivery. Recently, emerging evidence has spotlighted EVs in CRISPR delivery towards cancer treatment. In this review, we briefly introduce the biology and function of the CRISPR system and follow this with a summary of current delivery methods for CRISPR applications. We emphasize the recent progress in EV-mediated CRISPR editing for various cancer types and target genes. The reported strategies for constructing EV-CRISPR vectors, as well as their limitations, are discussed in detail. The review aims to throw light on the clinical potential of engineered EVs and encourage the expansion of our available toolkit to defeat cancer. Full article
(This article belongs to the Special Issue Advance in Exosomes in Tumors)
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Other

Jump to: Research, Review

15 pages, 2549 KiB  
Brief Report
Cross-Dressing of Multiple Myeloma Cells Mediated by Extracellular Vesicles Conveying MIC and ULBP Ligands Promotes NK Cell Killing
by Elisabetta Vulpis, Luisa Loconte, Chiara Cassone, Fabrizio Antonangeli, Giulio Caracciolo, Laura Masuelli, Francesca Fazio, Maria Teresa Petrucci, Cinzia Fionda, Alessandra Soriani, Cristina Cerboni, Marco Cippitelli, Angela Santoni and Alessandra Zingoni
Int. J. Mol. Sci. 2023, 24(11), 9467; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24119467 - 30 May 2023
Cited by 2 | Viewed by 1341
Abstract
Natural Killer (NK) cells are innate cytotoxic lymphoid cells that play a crucial role in cancer immunosurveillance. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed, or infected cells. The secretion of NKG2D ligands (NKG2DLs) [...] Read more.
Natural Killer (NK) cells are innate cytotoxic lymphoid cells that play a crucial role in cancer immunosurveillance. NKG2D is an activating receptor that binds to MIC and ULBP molecules typically induced on damaged, transformed, or infected cells. The secretion of NKG2D ligands (NKG2DLs) through protease-mediated cleavage or in an extracellular vesicle (EV) is a mode to control their cell surface expression and a mechanism used by cancer cells to evade NKG2D-mediated immunosurveillance. EVs are emerging as important players in mediating cell-to-cell communication due to their ability to transfer biological material to acceptor cells. Herein, we investigated the spreading of NKG2DLs of both MIC and ULBP molecules through the EV-mediated cross-dressing on multiple myeloma (MM) cells. We focused our attention on two MICA allelic variants, namely MICA*008 and MICA*019, representing the prototype of short and long MICA alleles, respectively, and on ULBP-1, ULBP-2, and ULBP-3. Our findings demonstrate that both ULBP and MICA ligands can be acquired from tumor cells through EVs enhancing NK cell recognition and killing. Moreover, besides MICA, EVs expressing ULBP-1 but not ULBP-2 and 3 were detected in bone marrow aspirates derived from a cohort of MM patients. Our findings shed light on the role of EV-associated MICA allelic variants and ULBP molecules in the modulation of NKG2D-mediated NK cell immunosurveillance in the tumor microenvironment. Moreover, the EV-mediated transfer of NKG2DLs could suggest novel therapeutic approaches based on the usage of engineered nanoparticles aimed at increasing cancer cell immunogenicity. Full article
(This article belongs to the Special Issue Advance in Exosomes in Tumors)
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