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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 2.0

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 March 2024) | Viewed by 9526

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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14 pages, 1951 KiB  
Article
Potential Protective Role of Melatonin in Benign Mammary Cells Reprogrammed by Extracellular Vesicles from Malignant Cells
by Caroline Procópio de Oliveira, Barbara Maria Frigieri, Heidge Fukumasu, Luiz Gustavo de Almeida Chuffa, Adriana Alonso Novais and Debora Aparecida Pires de Campos Zuccari
Biomedicines 2023, 11(10), 2837; https://doi.org/10.3390/biomedicines11102837 - 19 Oct 2023
Cited by 1 | Viewed by 1546
Abstract
(1) Background: Mammary neoplasms in female dogs share many similarities with the same tumor class in humans, rendering these animals a valuable preclinical model for studying novel therapies against breast cancer. The intricate role of extracellular vesicles (EVs), particularly exosomes, in breast carcinogenesis, [...] Read more.
(1) Background: Mammary neoplasms in female dogs share many similarities with the same tumor class in humans, rendering these animals a valuable preclinical model for studying novel therapies against breast cancer. The intricate role of extracellular vesicles (EVs), particularly exosomes, in breast carcinogenesis, by transferring specific proteins to recipient cells within the tumor microenvironment, underscores their significance. Melatonin, a hormone recognized for its antitumor effects, adds another layer of intrigue. (2) Methods: EVs obtained from the plasma of dogs diagnosed with mammary tumors were co cultivated with the benign epithelial lineage E-20 using DMEM. The experiment comprised four 24 h treatment groups: control, EVs, melatonin, and EVs + melatonin. A series of assays were conducted, including colony formation, proliferation, and cellular migration assessments. Furthermore, we conducted colony formation, proliferation, and cellular migration assays. We performed immunohistochemistry for proteins of the mTOR pathway, including mTOR and AKT. (3) Results: Exosomes alone significantly increased proliferation, migration, and colony formation rates and, upregulated the expression of mTOR and AKT proteins. However, when melatonin was added, a protective effect was observed. (4) Conclusions: These findings contributed to the use of melatonin to modulate EV-mediated signaling in the clinical veterinary oncology of mammary tumors. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer 2.0)
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17 pages, 2419 KiB  
Article
Lysine Acetylome of Breast Cancer-Derived Small Extracellular Vesicles Reveals Specific Acetylation Patterns for Metabolic Enzymes
by Zoran Minic, Yingxi Li, Nico Hüttmann, Gurcharan K. Uppal, Rochelle D’Mello and Maxim V. Berezovski
Biomedicines 2023, 11(4), 1076; https://doi.org/10.3390/biomedicines11041076 - 2 Apr 2023
Cited by 7 | Viewed by 2691
Abstract
Cancer-derived small extracellular vesicles have been proposed as promising potential biomarkers for diagnosis and prognosis of breast cancer (BC). We performed a proteomic study of lysine acetylation of breast cancer-derived small extracellular vesicles (sEVs) to understand the potential role of the aberrant acetylated [...] Read more.
Cancer-derived small extracellular vesicles have been proposed as promising potential biomarkers for diagnosis and prognosis of breast cancer (BC). We performed a proteomic study of lysine acetylation of breast cancer-derived small extracellular vesicles (sEVs) to understand the potential role of the aberrant acetylated proteins in the biology of invasive ductal carcinoma and triple-negative BC. Three cell lines were used as models for this study: MCF10A (non-metastatic), MCF7 (estrogen and progesterone receptor-positive, metastatic) and MDA-MB-231 (triple-negative, highly metastatic). For a comprehensive protein acetylation analysis of the sEVs derived from each cell line, acetylated peptides were enriched using the anti-acetyl-lysine antibody, followed by LC-MS/MS analysis. In total, there were 118 lysine-acetylated peptides, of which 22, 58 and 82 have been identified in MCF10A, MCF7 and MDA-MB-231 cell lines, respectively. These acetylated peptides were mapped to 60 distinct proteins and mainly identified proteins involved in metabolic pathways. Among the acetylated proteins identified in cancer-derived sEVs from MCF7 and MDA-MB-231 cell lines are proteins associated with the glycolysis pathway, annexins and histones. Five acetylated enzymes from the glycolytic pathway, present only in cancer-derived sEVs, were validated. These include aldolase (ALDOA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK1), enolase (ENO) and pyruvate kinase M1/2 (PKM). For three of these enzymes (ALDOA, PGK1 and ENO) the specific enzymatic activity was significantly higher in MDA-MB-231 when compared with MCF10A-derived sEVs. This study reveals that sEVs contain acetylated glycolytic metabolic enzymes that could be interesting potential candidates for early BC diagnostics. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer 2.0)
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18 pages, 4329 KiB  
Article
Interleukin-4 Receptor Targeting Peptide Decorated Extracellular Vesicles as a Platform for In Vivo Drug Delivery to Thyroid Cancer
by Prakash Gangadaran, Gowri Rangaswamy Gunassekaran, Ramya Lakshmi Rajendran, Ji Min Oh, Sri Murugan Poongkavithai Vadevoo, Ho Won Lee, Chae Moon Hong, Byungheon Lee, Jaetae Lee and Byeong-Cheol Ahn
Biomedicines 2022, 10(8), 1978; https://doi.org/10.3390/biomedicines10081978 - 15 Aug 2022
Cited by 14 | Viewed by 2664
Abstract
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been demonstrated to deliver therapeutic drugs in preclinical studies. However, their use is limited, as they lack the ability to specifically deliver drugs to tumor tissues in vivo. In the present study, we propose the [...] Read more.
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been demonstrated to deliver therapeutic drugs in preclinical studies. However, their use is limited, as they lack the ability to specifically deliver drugs to tumor tissues in vivo. In the present study, we propose the use of a targeting peptide, IL-4R-binding peptide (IL4RPep-1), to specifically deliver intravenously (i.v.) infused EVs to thyroid tumors. In vivo, a xenograft tumor model was treated with either the control peptide (NSSSVDK) or IL4RPep-1-Flamma; mice were fluorescently imaged (FLI) using an in vivo imaging system at 0–3 h post-treatment. EVs (labeled with DiD dye) were conjugated with IL4RPep-1 through a DOPE-NHS linker and administered to mice intravenously. FLI was performed 0–24 h post-injection, and the animals were sacrificed for further experiments. The morphology and size of EVs, the presence of EV markers such as CD63 and ALIX, and the absence of the markers GM130 and Cyto-C were confirmed. In vivo, FLI indicated an accumulation of i.v. injected IL4RPep-1-Flamma at the tumor site 90 min post-injection. No accumulation of NSSSVDK-Flamma was detected. In vivo, IL4RPep-1-EVs targeted the Cal-62 tumor 2 h post-injection. NSSSVDK-EVs were not even detected in the tumor 24 h post-injection. The quantification of FLI showed a significant accumulation of MSC-EVs in the tumor 2 h, 3 h, and 24 h post-injection. Furthermore, ex vivo imaging and an IF analysis confirmed the in vivo findings. Our results demonstrate the use of the IL4RPep-1 peptide as a targeting moiety of EVs for IL-4R-expressing anaplastic thyroid tumors. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer 2.0)
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Review

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11 pages, 687 KiB  
Review
Decoding Hidden Messengers: Proteomic Profiling of Exosomes in Mammary Cancer Research
by Adriana Alonso Novais, Guilherme Henrique Tamarindo, Luiz Gustavo de Almeida Chuffa and Debora Aparecida Pires de Campos Zuccari
Biomedicines 2023, 11(10), 2839; https://doi.org/10.3390/biomedicines11102839 - 19 Oct 2023
Cited by 3 | Viewed by 1759
Abstract
Cancer is a complex and heterogeneous disease, influenced by various factors that affect its progression and response to treatment. Although a histopathological diagnosis is crucial for identifying and classifying cancer, it may not accurately predict the disease’s development and evolution in all cases. [...] Read more.
Cancer is a complex and heterogeneous disease, influenced by various factors that affect its progression and response to treatment. Although a histopathological diagnosis is crucial for identifying and classifying cancer, it may not accurately predict the disease’s development and evolution in all cases. To address this limitation, liquid biopsy has emerged as a valuable tool, enabling a more precise and non-invasive analysis of cancer. Liquid biopsy can detect tumor DNA fragments, circulating tumor cells, and exosomes released by cancer cells into the bloodstream. Exosomes attracted significant attention in cancer research because of their specific protein composition, which can provide valuable insights into the disease. The protein profile of exosomes often differs from that of normal cells, reflecting the unique molecular characteristics of cancer. Analyzing these proteins can help identify cancer-associated markers that play important roles in tumor progression, invasion, and metastasis. Ongoing research and clinical validation are essential to advance and effectively utilize protein biomarkers in cancer. Nevertheless, their potential to improve diagnosis and treatment is highly promising. This review discusses several exosome proteins of interest in breast cancer, particularly focusing on studies conducted in mammary tissue and cell lines in humans and experimental animals. Unfortunately, studies conducted in canine species are scarce. This emphasis sheds light on the limited research available in this field. In addition, we present a curated selection of studies that explored exosomal proteins as potential biomarkers, aiming to achieve benefits in breast cancer diagnosis, prognosis, monitoring, and treatment. Full article
(This article belongs to the Special Issue Omics Approaches to Study Extracellular Vesicles for Diagnosis and Treatment of Cancer 2.0)
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