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Cancers
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The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis
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The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (15 October 2020) | Viewed by 22687

Special Issue Editor

Dr. M. Helena Vasconcelos

E-Mail Website
Guest Editor
1. FFUP – Faculdade de Farmácia da Universidade do Porto, 4050-313 Porto, Potugal
2. i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
Interests: cancer drug resistance; cancer multidrug resistance; intercellular transfer of drug resistance mediated by Extracellular Vesicles (EVs); new approaches to overcome drug resistance; drug-efflux pumps; escape from apoptosis; autophagy; metabolic alterations associated with drug resistance; tumour-microenvironment interactions; cancer stem cells; microRNAs; biomarkers of minimal residual disease and of drug resistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Cancers aims to bring together timely reviews and original research articles on the impact of Extracellular Vesicles on cancer progression and on cancer patient’s diagnosis. Topics may include but are not exclusively limited to studying the: i) impact of EVs in cancer progression and drug resistance; ii) role of EVs in the bi-directional intercellular communication between cancer cells and the tumor microenvironment; iii) cargo of EVs and their release, intercellular transfer and uptake; iv) search for EV-associated biomarkers of cancer diagnosis or prognosis.

Prof. Dr. M. Helena Vasconcelos
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. 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
  • cancer progression
  • hallmarks of cancer
  • cancer drug resistance
  • intercellular communication
  • EV-associated biomarkers of cancer diagnosis
  • EV-associated biomarkers of cancer prognosis
  • EV-associated biomarkers of minimal residual disease

Published Papers (6 papers)

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Research

Jump to: Review

20 pages, 3845 KiB  
Article
Detection of Tumor-Associated Membrane Receptors on Extracellular Vesicles from Non-Small Cell Lung Cancer Patients via Immuno-PCR
by Christiane Stiller, Kristina Viktorsson, Elizabeth Paz Gomero, Petra Hååg, Vasiliki Arapi, Vitaliy O. Kaminskyy, Caroline Kamali, Luigi De Petris, Simon Ekman, Rolf Lewensohn and Amelie Eriksson Karlström
Cancers 2021, 13(4), 922; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13040922 - 22 Feb 2021
Cited by 11 | Viewed by 3196
Abstract
Precision cancer medicine for non-small-cell lung cancer (NSCLC) has increased patient survival. Nevertheless, targeted agents towards tumor-associated membrane receptors only result in partial remission for a limited time, calling for approaches which allow longitudinal treatment monitoring. Rebiopsy of tumors in the lung is [...] Read more.
Precision cancer medicine for non-small-cell lung cancer (NSCLC) has increased patient survival. Nevertheless, targeted agents towards tumor-associated membrane receptors only result in partial remission for a limited time, calling for approaches which allow longitudinal treatment monitoring. Rebiopsy of tumors in the lung is challenging, and metastatic lesions may have heterogeneous signaling. One way ahead is to use liquid biopsies such as circulating tumor DNA or small extracellular vesicles (sEVs) secreted by the tumor into blood or other body fluids. Herein, an immuno-PCR-based detection of the tumor-associated membrane receptors EGFR, HER2, and IGF-1R on CD9-positive sEVs from NSCLC cells and pleural effusion fluid (PE) of NSCLC patients is developed utilizing DNA conjugates of antibody mimetics and affibodies, as detection agents. Results on sEVs purified from culture media of NSCLC cells treated with anti-EGFR siRNA, showed that the reduction of EGFR expression can be detected via immuno-PCR. Protein profiling of sEVs from NSCLC patient PE samples revealed the capacity to monitor EGFR, HER2, and IGF-1R with the immuno-PCR method. We detected a significantly higher EGFR level in sEVs derived from a PE sample of a patient with an EGFR-driven NSCLC adenocarcinoma than in sEVs from PE samples of non-EGFR driven adenocarcinoma patients or in samples from patients with benign lung disease. In summary, we have developed a diagnostic method for sEVs in liquid biopsies of cancer patients which may be used for longitudinal treatment monitoring to detect emerging bypassing resistance mechanisms in a noninvasive way. Full article
(This article belongs to the Special Issue The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis)
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18 pages, 3362 KiB  
Article
Is the Proteome of Bronchoalveolar Lavage Extracellular Vesicles a Marker of Advanced Lung Cancer?
by Ana Sofia Carvalho, Maria Carolina Strano Moraes, Chan Hyun Na, Ivo Fierro-Monti, Andreia Henriques, Sara Zahedi, Cristian Bodo, Erin M Tranfield, Ana Laura Sousa, Ana Farinho, Luís Vaz Rodrigues, Paula Pinto, Cristina Bárbara, Leonor Mota, Tiago Tavares de Abreu, Júlio Semedo, Susana Seixas, Prashant Kumar, Bruno Costa-Silva, Akhilesh Pandey and Rune Matthiesenadd Show full author list remove Hide full author list
Cancers 2020, 12(11), 3450; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113450 - 20 Nov 2020
Cited by 13 | Viewed by 3836
Abstract
Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking [...] Read more.
Acellular bronchoalveolar lavage (BAL) proteomics can partially separate lung cancer from non-lung cancer patients based on principal component analysis and multivariate analysis. Furthermore, the variance in the proteomics data sets is correlated mainly with lung cancer status and, to a lesser extent, smoking status and gender. Despite these advances BAL small and large extracellular vehicles (EVs) proteomes reveal aberrant protein expression in paracrine signaling mechanisms in cancer initiation and progression. We consequently present a case-control study of 24 bronchoalveolar lavage extracellular vesicle samples which were analyzed by state-of-the-art liquid chromatography-mass spectrometry (LC-MS). We obtained evidence that BAL EVs proteome complexity correlated with lung cancer stage 4 and mortality within two years´ follow-up (p value = 0.006). The potential therapeutic target DNMT3B complex is significantly up-regulated in tumor tissue and BAL EVs. The computational analysis of the immune and fibroblast cell markers in EVs suggests that patients who deceased within the follow-up period display higher marker expression indicative of innate immune and fibroblast cells (four out of five cases). This study provides insights into the proteome content of BAL EVs and their correlation to clinical outcomes. Full article
(This article belongs to the Special Issue The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis)
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18 pages, 3550 KiB  
Article
Cancer Alters the Metabolic Fingerprint of Extracellular Vesicles
by Mari Palviainen, Kirsi Laukkanen, Zeynep Tavukcuoglu, Vidya Velagapudi, Olli Kärkkäinen, Kati Hanhineva, Seppo Auriola, Annamari Ranki and Pia Siljander
Cancers 2020, 12(11), 3292; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113292 - 06 Nov 2020
Cited by 12 | Viewed by 3683
Abstract
Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts [...] Read more.
Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer. Full article
(This article belongs to the Special Issue The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis)
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Review

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23 pages, 5874 KiB  
Review
Immune Regulation by Dendritic Cell Extracellular Vesicles in Cancer Immunotherapy and Vaccines
by Irene Fernández-Delgado, Diego Calzada-Fraile and Francisco Sánchez-Madrid
Cancers 2020, 12(12), 3558; https://doi.org/10.3390/cancers12123558 - 28 Nov 2020
Cited by 34 | Viewed by 4832
Abstract
Extracellular vesicles (EVs) play a crucial role in intercellular communication as vehicles for the transport of membrane and cytosolic proteins, lipids, and nucleic acids including different RNAs. Dendritic cells (DCs)-derived EVs (DEVs), albeit variably, express major histocompatibility complex (MHC)-peptide complexes and co-stimulatory molecules [...] Read more.
Extracellular vesicles (EVs) play a crucial role in intercellular communication as vehicles for the transport of membrane and cytosolic proteins, lipids, and nucleic acids including different RNAs. Dendritic cells (DCs)-derived EVs (DEVs), albeit variably, express major histocompatibility complex (MHC)-peptide complexes and co-stimulatory molecules on their surface that enable the interaction with other immune cells such as CD8+ T cells, and other ligands that stimulate natural killer (NK) cells, thereby instructing tumor rejection, and counteracting immune-suppressive tumor microenvironment. Malignant cells oppose this effect by secreting EVs bearing a variety of molecules that block DCs function. For instance, tumor-derived EVs (TDEVs) can impair myeloid cell differentiation resulting in myeloid-derived suppressor cells (MDSCs) generation. Hence, the unique composition of EVs makes them suitable candidates for the development of new cancer treatment approaches including prophylactic vaccine targeting oncogenic pathogens, cancer vaccines, and cancer immunotherapeutics. We offer a perspective from both cell sides, DCs, and tumor cells, on how EVs regulate the antitumor immune response, and how this translates into promising therapeutic options by reviewing the latest advancement in DEV-based cancer therapeutics. Full article
(This article belongs to the Special Issue The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis)
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13 pages, 1232 KiB  
Review
Extracellular Vesicle Dissemination of Epidermal Growth Factor Receptor and Ligands and Its Role in Cancer Progression
by Thomas Frawley and Olga Piskareva
Cancers 2020, 12(11), 3200; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113200 - 30 Oct 2020
Cited by 20 | Viewed by 3037
Abstract
The epidermal growth factor receptor (EGFR) pathway functions through the autocrine or paracrine activation of cellular EGFR by a number of transmembrane ligands. Amplified or mutant EGFR can lead to tumour formation due to increased cell proliferation, growth, migration and survival signals. These [...] Read more.
The epidermal growth factor receptor (EGFR) pathway functions through the autocrine or paracrine activation of cellular EGFR by a number of transmembrane ligands. Amplified or mutant EGFR can lead to tumour formation due to increased cell proliferation, growth, migration and survival signals. These oncogenic effects were thought to be confined to aberrant cells hosting genetic alterations in EGFR. However, in the past decade, numerous studies identified that tumour cells could harness extracellular vesicles (EVs) to disseminate EGFR, mutant EGFR, phosphorylated EGFR and EGFR ligands to local and distant cells. This functions to impart a pro-tumourigenic phenotype in recipient cells. EVs play an essential role in intracellular communication, through receptor signalling or the release of their intra-vesicular content into recipient cells. This review will discuss the role of EVs delivering EGFR or EGFR ligands either to or from tumour cells and how this can promote metastases, pre-metastatic niche formation, osteoclastogenesis, angiogenesis and immune modulation in cancer. We will examine how circulating EVs positive for EGFR may be exploited as diagnostic, prognostic or therapeutic markers in cancers including breast, lung, glioblastoma, ovarian and prostate. Finally, we will explore recent breakthroughs in bio-engineering EVs with EGFR targeting abilities for targeted drug delivery. Full article
(This article belongs to the Special Issue The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis)
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36 pages, 785 KiB  
Review
Cancer Extracellular Vesicles: Next-Generation Diagnostic and Drug Delivery Nanotools
by Stefano Palazzolo, Lorenzo Memeo, Mohamad Hadla, Fahriye Duzagac, Agostino Steffan, Tiziana Perin, Vincenzo Canzonieri, Tiziano Tuccinardi, Isabella Caligiuri and Flavio Rizzolio
Cancers 2020, 12(11), 3165; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113165 - 28 Oct 2020
Cited by 19 | Viewed by 3245
Abstract
Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role [...] Read more.
Nanosized extracellular vesicles (EVs) with dimensions ranging from 100 to 1000 nm are continuously secreted from different cells in their extracellular environment. They are able to encapsulate and transfer various biomolecules, such as nucleic acids, proteins, and lipids, that play an essential role in cell‒cell communication, reflecting a novel method of extracellular cross-talk. Since EVs are present in large amounts in most bodily fluids, challengeable hypotheses are analyzed to unlock their potential roles. Here, we review EVs by discussing their specific characteristics (structure, formation, composition, and isolation methods), focusing on their key role in cell biology. Furthermore, this review will summarize the biomedical applications of EVs, in particular those between 30 and 150 nm (like exosomes), as next-generation diagnostic tools in liquid biopsy for cancer and as novel drug delivery vehicles. Full article
(This article belongs to the Special Issue The Impact of Extracellular Vesicles in Cancer Progression and Diagnosis)
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