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Exosomes in Cancer Diagnosis and Therapy 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 21174

Special Issue Editor

Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Interests: cancer epigenetics; metastasis; cancer drug resistance; tumor microenvironment; miRNA; non-coding RNAs; cancer stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Exosomes are the smallest type of extracellular vesicles that play a role in the communication between cells. They act as cargo carriers, with their cargo consisting of many molecules derived from the cells that they originate from. Among other molecules, proteins, RNA, microRNAs, non-coding RNAs. etc. have generated particular interest among researchers as their exosome-mediated transfer to recipient cells is believed to confer many survival advantages. Exosomes can influence immune responses and processes as diverse as angiogenesis, metastasis, drug resistance, and metastasis. Thus, their potential exploitation as therapeutic targets has been advocated. At the same time, exosomes have been detected in various biological fluids, such as blood, urine, and cerebrospinal fluids, thus pointing to their use in the diagnosis of human cancers. This Special Issue covers all the topics relevant to the validation and/or targeting of exosomes in human cancers.

Dr. Aamir Ahmad
Guest Editor

Manuscript Submission Information

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Keywords

  • exosomes
  • CD9
  • CD81
  • cancer
  • diagnostic biomarkers
  • cancer therapy
  • angiogenesis
  • drug resistance
  • metastasis
  • mRNA
  • miRNA
  • non-coding RNAs

Related Special Issue

Published Papers (7 papers)

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Research

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14 pages, 2045 KiB  
Article
CA-IX-Expressing Small Extracellular Vesicles (sEVs) Are Released by Melanoma Cells under Hypoxia and in the Blood of Advanced Melanoma Patients
by Marta Venturella, Alessandro Falsini, Federica Coppola, Gaia Giuntini, Fabio Carraro, Davide Zocco, Antonio Chiesi and Antonella Naldini
Int. J. Mol. Sci. 2023, 24(7), 6122; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24076122 - 24 Mar 2023
Cited by 2 | Viewed by 1445
Abstract
Cutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found [...] Read more.
Cutaneous melanoma is a highly aggressive skin cancer, with poor prognosis. The tumor microenvironment is characterized by areas of hypoxia. Carbonic anhydrase IX (CA-IX) is a marker of tumor hypoxia and its expression is regulated by hypoxia-inducible factor-1 (HIF-1). CA-IX has been found to be highly expressed in invasive melanomas. In this study, we investigated the effects of hypoxia on the release of small extracellular vesicles (sEVs) in two melanoma in vitro models. We demonstrated that melanoma cells release sEVs under both normoxic and hypoxic conditions, but only hypoxia-induced sEVs express CA-IX mRNA and protein. Moreover, we optimized an ELISA assay to provide evidence for CA-IX protein expression on the membranes of the sEVs. These CA-IX-positive sEVs may be exploited as potential biomarkers for liquid biopsy. Full article
(This article belongs to the Special Issue Exosomes in Cancer Diagnosis and Therapy 2.0)
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29 pages, 4478 KiB  
Article
Adipose Tissue-Derived Extracellular Vesicles Contribute to Phenotypic Plasticity of Prostate Cancer Cells
by Allison Mathiesen, Bronson Haynes, Ryan Huyck, Michael Brown and Anca Dobrian
Int. J. Mol. Sci. 2023, 24(2), 1229; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021229 - 08 Jan 2023
Cited by 2 | Viewed by 2075
Abstract
Metastatic prostate cancer is one of the leading causes of male cancer deaths in the western world. Obesity significantly increases the risk of metastatic disease and is associated with a higher mortality rate. Systemic chronic inflammation can result from a variety of conditions, [...] Read more.
Metastatic prostate cancer is one of the leading causes of male cancer deaths in the western world. Obesity significantly increases the risk of metastatic disease and is associated with a higher mortality rate. Systemic chronic inflammation can result from a variety of conditions, including obesity, where adipose tissue inflammation is a major contributor. Adipose tissue endothelial cells (EC) exposed to inflammation become dysfunctional and produce a secretome, including extracellular vesicles (EV), that can impact function of cells in distant tissues, including malignant cells. The aim of this study was to explore the potential role of EVs produced by obese adipose tissue and the ECs exposed to pro-inflammatory cytokines on prostate cancer phenotypic plasticity in vitro. We demonstrate that PC3ML metastatic prostate cancer cells exposed to EVs from adipose tissue ECs and to EVs from human adipose tissue total explants display reduced invasion and increased proliferation. The latter functional changes could be attributed to the EV miRNA cargo. We also show that the functional shift is TWIST1-dependent and is consistent with mesenchymal-to-epithelial transition, which is key to establishment of secondary tumor growth. Understanding the complex effects of EVs on prostate cancer cells of different phenotypes is key before their intended use as therapeutics. Full article
(This article belongs to the Special Issue Exosomes in Cancer Diagnosis and Therapy 2.0)
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25 pages, 3646 KiB  
Article
Effect of Pre-Processing Storage Condition of Cell Culture-Conditioned Medium on Extracellular Vesicles Derived from Human Umbilical Cord-Derived Mesenchymal Stromal Cells
by Adrienne Wright, Orman L. Snyder, Lane K. Christenson, Hong He and Mark L. Weiss
Int. J. Mol. Sci. 2022, 23(14), 7716; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147716 - 13 Jul 2022
Cited by 3 | Viewed by 2635
Abstract
EVs can be isolated from a conditioned medium derived from mesenchymal stromal cells (MSCs), yet the effect of the pre-processing storage condition of the cell culture-conditioned medium prior to EV isolation is not well-understood. Since MSCs are already in clinical trials, the GMP-grade [...] Read more.
EVs can be isolated from a conditioned medium derived from mesenchymal stromal cells (MSCs), yet the effect of the pre-processing storage condition of the cell culture-conditioned medium prior to EV isolation is not well-understood. Since MSCs are already in clinical trials, the GMP-grade of the medium which is derived from their manufacturing might have the utility for preclinical testing, and perhaps, for clinical translation, so the impact of pre-processing storage condition on EV isolation is a barrier for utilization of this MSC manufacturing by-product. To address this problem, the effects of the pre-processing storage conditions on EV isolation, characterization, and function were assessed using a conditioned medium (CM) derived from human umbilical cord-derived MSCs (HUC-MSCs). Hypothesis: The comparison of three different pre-processing storage conditions of CM immediately processed for EV isolation would reveal differences in EVs, and thus, suggest an optimal pre-processing storage condition. The results showed that EVs derived from a CM stored at room temperature, 4 °C, −20 °C, and −80 °C for at least one week were not grossly different from EVs isolated from the CM immediately after collection. EVs derived from an in pre-processing −80 °C storage condition had a significantly reduced polydispersity index, and significantly enhanced dot blot staining, but their zeta potential, hydrodynamic size, morphology and size in transmission electron microscopy were not significantly different from EVs derived from the CM immediately processed for isolation. There was no impact of pre-processing storage condition on the proliferation of sarcoma cell lines exposed to EVs. These data suggest that the CM produced during GMP-manufacturing of MSCs for clinical applications might be stored at −80 °C prior to EV isolation, and this may enable production scale-up, and thus, and enable preclinical and clinical testing, and EV lot qualification. Full article
(This article belongs to the Special Issue Exosomes in Cancer Diagnosis and Therapy 2.0)
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20 pages, 3425 KiB  
Article
Supplementation with Serum-Derived Extracellular Vesicles Reinforces Antitumor Immunity Induced by Cryo-Thermal Therapy
by Yinuo Cen, Yue Lou, Junjun Wang, Shicheng Wang, Peng Peng, Aili Zhang and Ping Liu
Int. J. Mol. Sci. 2021, 22(20), 11021; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222011021 - 13 Oct 2021
Cited by 3 | Viewed by 1807
Abstract
Effective cancer therapies should reshape immunosuppression and trigger antitumor immunity. Previously, we developed a novel cryo-thermal therapy through applying local rapid cooling followed by rapid heating of tumor tissue. It could not only ablate local tumors, but also, subsequently, induce systemic long-term antitumor [...] Read more.
Effective cancer therapies should reshape immunosuppression and trigger antitumor immunity. Previously, we developed a novel cryo-thermal therapy through applying local rapid cooling followed by rapid heating of tumor tissue. It could not only ablate local tumors, but also, subsequently, induce systemic long-term antitumor immunity. Hyperthermia can induce the release of extracellular vesicles (EVs) to stimulate antitumor immunity. We examine whether EVs are released after cryo-thermal therapy and whether they could improve the efficacy of cryo-thermal therapy in the 4T1 model. In this study, serum extracellular vesicles (sEVs) are isolated and characterized 3 h after cryo-thermal therapy of subcutaneous tumors. sEV phagocytosis is observed in vitro and in vivo by using laser confocal microscopy and flow cytometry. After cryo-thermal therapy, sEVs are administered to mice via the tail vein, and changes in immune cells are investigated by using flow cytometry. After cryo-thermal therapy, a large number of sEVs are released to the periphery carrying danger signals and tumor antigens, and these sEVs could be phagocytosed by peripheral blood monocytes and differentiated macrophages. After cryo-thermal therapy, supplementation with sEVs released after treatment promotes the differentiation of myeloid-derived suppressor cells (MDSCs), monocytes into macrophages and CD4+ T cells into the Th1 subtype, as well as prolonging the long-term survival of the 4T1 subcutaneous tumor-bearing mice. sEVs released after cryo-thermal tumor treatment could clinically serve as an adjuvant in subsequent cryo-thermal therapy to improve the therapeutic effects on malignant tumors. Full article
(This article belongs to the Special Issue Exosomes in Cancer Diagnosis and Therapy 2.0)
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Review

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20 pages, 1313 KiB  
Review
The Therapeutic Potential of Milk Extracellular Vesicles on Colorectal Cancer
by Manal A. Babaker, Fadwa A. Aljoud, Faris Alkhilaiwi, Abdulrahman Algarni, Asif Ahmed, Mohammad Imran Khan, Islam M. Saadeldin and Faisal A. Alzahrani
Int. J. Mol. Sci. 2022, 23(12), 6812; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23126812 - 18 Jun 2022
Cited by 20 | Viewed by 3530
Abstract
Colorectal cancer remains one of the leading prevalent cancers in the world and is the fourth most common cause of death from cancer. Unfortunately, the currently utilized chemotherapies fail in selectively targeting cancer cells and cause harm to healthy cells, which results in [...] Read more.
Colorectal cancer remains one of the leading prevalent cancers in the world and is the fourth most common cause of death from cancer. Unfortunately, the currently utilized chemotherapies fail in selectively targeting cancer cells and cause harm to healthy cells, which results in profound side effects. Researchers are focused on developing anti-cancer targeted medications, which is essential to making them safer, more effective, and more selective and to maximizing their therapeutic benefits. Milk-derived extracellular vesicles (EVs) from camels and cows have attracted much attention as a natural substitute product that effectively suppresses a wide range of tumor cells. This review sheds light on the biogenesis, methods of isolation, characterization, and molecular composition of milk EVs as well as the therapeutic potentials of milk EVs on colorectal cancer. Full article
(This article belongs to the Special Issue Exosomes in Cancer Diagnosis and Therapy 2.0)
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14 pages, 871 KiB  
Review
Exosome-Mediated Response to Cancer Therapy: Modulation of Epigenetic Machinery
by Mohammad Imran Khan, Reem K. M. E. Alsayed, Hani Choudhry and Aamir Ahmad
Int. J. Mol. Sci. 2022, 23(11), 6222; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116222 - 02 Jun 2022
Cited by 10 | Viewed by 2905
Abstract
Exosomes, the extracellular vesicles produced in the endosomal compartments, facilitate the transportation of proteins as well as nucleic acids. Epigenetic modifications are now considered important for fine-tuning the response of cancer cells to various therapies, and the acquired resistance against targeted therapies often [...] Read more.
Exosomes, the extracellular vesicles produced in the endosomal compartments, facilitate the transportation of proteins as well as nucleic acids. Epigenetic modifications are now considered important for fine-tuning the response of cancer cells to various therapies, and the acquired resistance against targeted therapies often involves dysregulated epigenetic modifications. Depending on the constitution of their cargo, exosomes can affect several epigenetic events, thus impacting post-transcriptional regulations. Thus, a role of exosomes as facilitators of epigenetic modifications has come under increased scrutiny in recent years. Exosomes can deliver methyltransferases to recipient cells and, more importantly, non-coding RNAs, particularly microRNAs (miRNAs), represent an important exosome cargo that can affect the expression of several oncogenes and tumor suppressors, with a resulting impact on cancer therapy resistance. Exosomes often harbor other non-coding RNAs, such as long non-coding RNAs and circular RNAs that support resistance. The exosome-mediated transfer of all this cargo between cancer cells and their surrounding cells, especially tumor-associated macrophages and cancer-associated fibroblasts, has a profound effect on the sensitivity of cancer cells to several chemotherapeutics. This review focuses on the exosome-induced modulation of epigenetic events with resulting impact on sensitivity of cancer cells to various therapies, such as, tamoxifen, cisplatin, gemcitabine and tyrosine kinase inhibitors. A better understanding of the mechanisms by which exosomes can modulate response to therapy in cancer cells is critical for the development of novel therapeutic strategies to target cancer drug resistance. Full article
(This article belongs to the Special Issue Exosomes in Cancer Diagnosis and Therapy 2.0)
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23 pages, 1704 KiB  
Review
The Role of Exosomes and Their Applications in Cancer
by Yuju Zhou, Ying Zhang, Huan Gong, Siqi Luo and Yan Cui
Int. J. Mol. Sci. 2021, 22(22), 12204; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212204 - 11 Nov 2021
Cited by 62 | Viewed by 5750
Abstract
Exosomes are very small extracellular vesicles secreted by multiple cell types and are extensively distributed in various biological fluids. Recent research indicated that exosomes can participate in regulating the tumor microenvironment and impacting tumor proliferation and progression. Due to the extensive enrollment in [...] Read more.
Exosomes are very small extracellular vesicles secreted by multiple cell types and are extensively distributed in various biological fluids. Recent research indicated that exosomes can participate in regulating the tumor microenvironment and impacting tumor proliferation and progression. Due to the extensive enrollment in cancer development, exosomes have become a focus of the search for a new therapeutic method for cancer. Exosomes can be utilized for the therapeutic delivery of small molecules, proteins and RNAs to target cancer cells with a high efficiency. Exosome-carried proteins, lipids and nucleic acids are being tested as promising biomarkers for cancer diagnosis and prognosis, even as potential treatment targets for cancer. Moreover, different sources of exosomes exhibit multiple performances in cancer applications. In this review, we elaborate on the specific mechanism by which exosomes affect the communication between tumors and the microenvironment and state the therapeutic and diagnostic applications of exosomes in cancers. Full article
(This article belongs to the Special Issue Exosomes in Cancer Diagnosis and Therapy 2.0)
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