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Biomedicines
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Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment...
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Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 17399

Special Issue Editor

Dr. Zoran Minic

E-Mail Website
Guest Editor
Department of Chemistry and Biomolecular Sciences, John L. Holmes Mass Spectrometry Facility, Faculty of Science, University of Ottawa, Ottawa, ON K1N6N5, Canada
Interests: extracellular vesicles; breast cancer; mass spectrometry; proteomics; phosphoproteomics; metabolomics; bioinformatics; biomarker
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer continues to be one of the leading causes of mortality worldwide. Advancements in our understanding of cancer progression, as well as novel detection and treatment strategies are constantly being sought after. Within the last decade, extracellular vesicles (EVs) have been recognized as a new mechanism of intercellular communication through the delivery of bioactive molecules such as proteins, metabolites, lipids, and nucleic acids, including messenger RNAs (mRNAs) and microRNAs (miRNAs). Their essential role in cancer biology has been highlighted in several recent studies. Cancer cell-derived EVs promote tumor progression by modulating the immune response, reprogramming the tumor microenvironment, and stimulating metastasis. Profiling the contents of EVs may further elucidate their role in cancer progression, early detection, and identification of therapeutic targets. New advancements in omics-based techniques such as genomics, transcriptomics, proteomics, and metabolomics, have contributed to a deeper understanding of molecular mechanisms through which EVs influence cancer biology. Therefore, the purpose of this Special Issue is to publish omics-based approaches studying extracellular vesicles to advance diagnosis and treatment of cancer on a molecular level.

Dr. Zoran Minic
Guest Editor

Manuscript Submission Information

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Keywords

  • Cancer
  • Extracellular vesicles
  • Genetics
  • Transcriptomics
  • Proteomics
  • Metabolomics
  • Bioinformatics
  • System biology
  • Biomarkers
  • Therapeutic targets

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Related Special Issue

Published Papers (4 papers)

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Research

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17 pages, 3434 KiB  
Article
Phosphoproteomic Analysis of Breast Cancer-Derived Small Extracellular Vesicles Reveals Disease-Specific Phosphorylated Enzymes
by Zoran Minic, Nico Hüttmann, Suttinee Poolsup, Yingxi Li, Vanessa Susevski, Emil Zaripov and Maxim V. Berezovski
Biomedicines 2022, 10(2), 408; https://doi.org/10.3390/biomedicines10020408 - 9 Feb 2022
Cited by 13 | Viewed by 4300
Abstract
Small membrane-derived extracellular vesicles have been proposed as participating in several cancer diseases, including breast cancer (BC). We performed a phosphoproteomic analysis of breast cancer-derived small extracellular vesicles (sEVs) to provide insight into the molecular and cellular regulatory mechanisms important for breast cancer [...] Read more.
Small membrane-derived extracellular vesicles have been proposed as participating in several cancer diseases, including breast cancer (BC). We performed a phosphoproteomic analysis of breast cancer-derived small extracellular vesicles (sEVs) to provide insight into the molecular and cellular regulatory mechanisms important for breast cancer tumor progression and metastasis. We examined three cell line models for breast cancer: MCF10A (non-malignant), MCF7 (estrogen and progesterone receptor-positive, metastatic), and MDA-MB-231 (triple-negative, highly metastatic). To obtain a comprehensive overview of the sEV phosphoproteome derived from each cell line, effective phosphopeptide enrichment techniques IMAC and TiO2, followed by LC-MS/MS, were performed. The phosphoproteome was profiled to a depth of 2003 phosphopeptides, of which 207, 854, and 1335 were identified in MCF10A, MCF7, and MDA-MB-231 cell lines, respectively. Furthermore, 2450 phosphorylation sites were mapped to 855 distinct proteins, covering a wide range of functions. The identified proteins are associated with several diseases, mostly related to cancer. Among the phosphoproteins, we validated four enzymes associated with cancer and present only in sEVs isolated from MCF7 and MDA-MB-231 cell lines: ATP citrate lyase (ACLY), phosphofructokinase-M (PFKM), sirtuin-1 (SIRT1), and sirtuin-6 (SIRT6). With the exception of PFKM, the specific activity of these enzymes was significantly higher in MDA-MB-231 when compared with MCF10A-derived sEVs. This study demonstrates that sEVs contain functional metabolic enzymes that could be further explored for their potential use in early BC diagnostic and therapeutic applications. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer)
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15 pages, 1688 KiB  
Article
Breast Cancer-Derived Microvesicles Are the Source of Functional Metabolic Enzymes as Potential Targets for Cancer Therapy
by Yousef Risha, Vanessa Susevski, Nico Hüttmann, Suttinee Poolsup, Zoran Minic and Maxim V. Berezovski
Biomedicines 2021, 9(2), 107; https://doi.org/10.3390/biomedicines9020107 - 22 Jan 2021
Cited by 8 | Viewed by 3506
Abstract
Membrane-derived extracellular vesicles, referred to as microvesicles (MVs), have been proposed to participate in several cancer diseases. In this study, MV fractions were isolated by differential ultracentrifugation from a metastatic breast cancer (BC) cell line MDA-MB-231 and a non-cancerous breast cell line MCF10A, [...] Read more.
Membrane-derived extracellular vesicles, referred to as microvesicles (MVs), have been proposed to participate in several cancer diseases. In this study, MV fractions were isolated by differential ultracentrifugation from a metastatic breast cancer (BC) cell line MDA-MB-231 and a non-cancerous breast cell line MCF10A, then analyzed by nano-liquid chromatography coupled to tandem mass spectrometry. A total of 1519 MV proteins were identified from both cell lines. The data obtained were compared to previously analyzed proteins from small extracellular vesicles (sEVs), revealing 1272 proteins present in both MVs and sEVs derived from the MDA-MB-231 cell line. Among the 89 proteins unique to MDA-MB-231 MVs, three enzymes: ornithine aminotransferase (OAT), transaldolase (TALDO1) and bleomycin hydrolase (BLMH) were previously proposed as cancer therapy targets. These proteins were enzymatically validated in cells, sEVs, and MVs derived from both cell lines. The specific activity of OAT and TALDO1 was significantly higher in MDA-MB-231-derived MVs than in MCF10A MVs. BLMH was highly expressed in MDA-MB-231-derived MVs, compared to MCF10A MVs. This study shows that MVs carry functional metabolic enzymes and provides a framework for future studies of their biological role in BC and potential in therapeutic applications. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer)
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9 pages, 1461 KiB  
Article
Comparison of Circulating Tumour DNA and Extracellular Vesicle DNA by Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers of Disease in a Breast Cancer Patient
by Olivia Ruhen, Bob Mirzai, Michael E. Clark, Bella Nguyen, Carlos Salomon, Wendy Erber and Katie Meehan
Biomedicines 2021, 9(1), 14; https://doi.org/10.3390/biomedicines9010014 - 25 Dec 2020
Cited by 15 | Viewed by 3050
Abstract
There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As [...] Read more.
There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both ctDNA and EV DNA from a patient with breast cancer. Of the 52 CNVs identified in tumour DNA, 36 (69%) were detected in at least one ctDNA sample and 13 (25%) in at least one EV DNA sample. The number of detectable variants in ctDNA and EV DNA increased over the natural history of the patient’s disease, which was associated with progression to cerebral metastases. This case study demonstrates that, while CNVs are detectable in patient EV DNA, ctDNA has greater sensitivity than EV DNA for serial monitoring of breast cancer. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer)
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Review

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14 pages, 715 KiB  
Review
The Role of Exosomes in Breast Cancer Diagnosis
by Claudia Piombino, Ilenia Mastrolia, Claudia Omarini, Olivia Candini, Massimo Dominici, Federico Piacentini and Angela Toss
Biomedicines 2021, 9(3), 312; https://doi.org/10.3390/biomedicines9030312 - 18 Mar 2021
Cited by 21 | Viewed by 5819
Abstract
The importance of molecular re-characterization of metastatic disease with the purpose of monitoring tumor evolution has been acknowledged in numerous clinical guidelines for the management of advanced malignancies. In this context, an attractive alternative to overcome the limitations of repeated tissue sampling is [...] Read more.
The importance of molecular re-characterization of metastatic disease with the purpose of monitoring tumor evolution has been acknowledged in numerous clinical guidelines for the management of advanced malignancies. In this context, an attractive alternative to overcome the limitations of repeated tissue sampling is represented by the analysis of peripheral blood samples as a ‘liquid biopsy’. In recent years, liquid biopsies have been studied for the early diagnosis of cancer, the monitoring of tumor burden, tumor heterogeneity and the emergence of molecular resistance, along with the detection of minimal residual disease. Interestingly, liquid biopsy consents the analysis of circulating tumor cells, circulating tumor DNA and extracellular vesicles (EVs). In particular, EVs play a crucial role in cell communication, carrying transmembrane and nonmembrane proteins, as well as metabolites, lipids and nucleic acids. Of all EVs, exosomes mirror the biological fingerprints of the parental cells from which they originate, and therefore, are considered one of the most promising predictors of early cancer diagnosis and treatment response. The present review discusses current knowledge on the possible applications of exosomes in breast cancer (BC) diagnosis, with a focus on patients at higher risk. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer)
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