The versatile roles and clinical implications of exosomal mRNAs and microRNAs in cancer

Extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies, are nanosized structures that are secreted by various cells and act as important mediators in intercellular communication. Recent studies have shown that exosomes carrying bioactive molecules are generated from multivesicular bodies and are present in various body fluids. mRNAs and microRNAs (miRNAs) are encapsulated in exosomes and have been found to be involved in multiple pathophysiological processes. Here, we provide a review of tumor-associated exosomal mRNAs and miRNAs and their roles in metastasis and drug resistance. In particular, we emphasize their clinical application potential as diagnostic and prognostic biomarkers of cancer and in cancer therapy.

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Tracheal tube fusion in Drosophila involves release of extracellular vesicles from multivesicular bodies

Journal of Cell Science ◽

10.1242/jcs.259590 ◽

2022 ◽

Author(s):

Carolina Camelo ◽

Anna Körte ◽

Thea Jacobs ◽

Stefan Luschnig

Keyword(s):

Tracheal Tube ◽

Extracellular Vesicles ◽

Intercellular Communication ◽

Cultured Cells ◽

Multivesicular Bodies ◽

Tracheal Lumen ◽

Luminal Membrane ◽

Tip Cells ◽

Drosophila Embryos

Extracellular vesicles (EVs) comprise diverse types of cell-released membranous structures that are thought to play important roles in intercellular communication. While the formation and functions of EVs have been investigated extensively in cultured cells, studies of EVs in vivo have remained scarce. We report here that EVs are present in the developing lumen of tracheal tubes in Drosophila embryos. We defined two distinct EV subpopulations, one of which contains the Munc13-4 homologue Staccato (Stac) and is spatially and temporally associated with tracheal tube fusion (anastomosis) events. The formation of Stac-positive luminal EVs depends on the tracheal tip-cell-specific GTPase Arl3, which is also required for the formation of Stac-positive multivesicular bodies, suggesting that Stac-EVs derive from fusion of Stac-MVBs with the luminal membrane in tip cells during anastomosis formation. The GTPases Rab27 and Rab35 cooperate downstream of Arl3 to promote Stac-MVB formation and tube fusion. We propose that Stac-MVBs act as membrane reservoirs that facilitate tracheal lumen fusion in a process regulated by Arl3, Rab27, Rab35, and Stac/Munc13-4.

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Extracellular vesicles-mediated intercellular communication: roles in the tumor microenvironment and anti-cancer drug resistance

Molecular Cancer ◽

10.1186/s12943-019-0965-7 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 53

Author(s):

Selma Maacha ◽

Ajaz A. Bhat ◽

Lizandra Jimenez ◽

Afsheen Raza ◽

Mohammad Haris ◽

...

Keyword(s):

Drug Resistance ◽

Tumor Microenvironment ◽

Extracellular Vesicles ◽

Intercellular Communication ◽

Cancer Drug ◽

Cancer Drug Resistance ◽

Anti Cancer

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Extracellular Vesicles Derived From Citrus sinensis Modulate Inflammatory Genes and Tight Junctions in a Human Model of Intestinal Epithelium

Frontiers in Nutrition ◽

10.3389/fnut.2021.778998 ◽

2021 ◽

Vol 8 ◽

Author(s):

Stefania Paola Bruno ◽

Alessandro Paolini ◽

Valentina D'Oria ◽

Angelo Sarra ◽

Simona Sennato ◽

...

Keyword(s):

Tight Junctions ◽

Extracellular Vesicles ◽

Intestinal Epithelium ◽

Intercellular Communication ◽

Citrus Sinensis ◽

Well Being ◽

Bioactive Molecules ◽

Human Model ◽

Biological Processes ◽

Inflammatory Stimuli

It is widely acknowledged that mammalian exosomes (or extracellular vesicles), have a key role in intercellular communication, owing to the presence of various bioactive molecules such as lipids, proteins, and microRNAs within their inner compartment. Most recently, the discovery of extracellular vesicles isolated from edible plants (such as vegetables and fruits) and their similarity in terms of size and content with exosomes has opened new perspectives on possible intercellular communication and regulation of important biological processes in which these vesicles are involved. It is also well-known that a balanced diet rich of fruits and vegetables (i.e., the Mediterranean diet) can contribute to maintain a “healthy gut” by preserving the intestinal epithelial barrier integrity and avoid that inflammatory stimuli that can alter homeostasis. In our study, we optimized a method to isolate extracellular vesicles from the orange juice (Citrus sinensis) (CS-EVs), and we characterized their morphology and behavior when in contact with the intestinal epithelium. We showed that CS-EVs are stable in a simulated gastrointestinal environment and are absorbed by intestinal cells without toxic effects, as expected. Furthermore, we demonstrated that CS-EVs can alter the gene expression of several genes involved in inflammation (i.e., ICAM1 and HMOX-1) and tight junctions (i.e., OCLN, CLDN1, and MLCK), contributing to limit inflammatory stimuli and restore a functional barrier by increasing the tight junction OCLN protein. Therefore, our study emphasizes the relevant role of fruit-derived extracellular vesicles in modulating important biological processes and maintaining a healthy intestinal epithelium, ultimately promoting human health and well-being.

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The Roles of Extracellular Vesicles in Malignant Melanoma

Cells ◽

10.3390/cells10102740 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2740

Author(s):

Ying-Chen Cheng ◽

Yu-An Chang ◽

Yi-Jen Chen ◽

Hsu-Min Sung ◽

Ivan Bogeski ◽

...

Keyword(s):

Drug Resistance ◽

Endothelial Cells ◽

Malignant Melanoma ◽

Extracellular Vesicles ◽

Immune Cells ◽

Therapeutic Strategies ◽

Bioactive Molecules ◽

Different Types ◽

Novel Therapeutic Strategies ◽

Novel Therapeutic

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.

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Recent Advances in Exosome-Based Drug Delivery for Cancer Therapy

Cancers ◽

10.3390/cancers13174435 ◽

2021 ◽

Vol 13 (17) ◽

pp. 4435

Author(s):

Hyosuk Kim ◽

Hochung Jang ◽

Haeun Cho ◽

Jiwon Choi ◽

Kwang Yeon Hwang ◽

...

Keyword(s):

Drug Delivery ◽

Cancer Therapy ◽

Nucleic Acids ◽

Extracellular Vesicles ◽

Targeted Delivery ◽

Drug Delivery Systems ◽

Therapeutic Agents ◽

Bioactive Molecules ◽

Chemotherapeutic Drugs ◽

Efficient Delivery

Exosomes are a class of extracellular vesicles, with a size of about 100 nm, secreted by most cells and carrying various bioactive molecules such as nucleic acids, proteins, and lipids, and reflect the biological status of parent cells. Exosomes have natural advantages such as high biocompatibility and low immunogenicity for efficient delivery of therapeutic agents such as chemotherapeutic drugs, nucleic acids, and proteins. In this review, we introduce the latest explorations of exosome-based drug delivery systems for cancer therapy, with particular focus on the targeted delivery of various types of cargoes.

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Extracellular vesicles: An overview of biogenesis, function, and role in breast cancer

Tumor Biology ◽

10.1177/1010428317691182 ◽

2017 ◽

Vol 39 (2) ◽

pp. 101042831769118 ◽

Cited By ~ 17

Author(s):

Quan Bin Zha ◽

Yu Feng Yao ◽

Zhao Jun Ren ◽

Xiu Juan Li ◽

Jin Hai Tang

Keyword(s):

Breast Cancer ◽

Cancer Therapy ◽

Extracellular Vesicles ◽

Intercellular Communication ◽

Therapeutic Approach ◽

Active Role ◽

Therapeutic Agents ◽

Breast Fluid ◽

Breast Physiology ◽

Potential Use

Extracellular vesicles have emerged as important mediators of intercellular communication and play an active role in cancer, including breast cancer. Despite limited studies, initial observations suggest that these vesicles are important in breast physiology and pathophysiology. We here, in brief, describe their potential use as future biomarkers and therapeutic agents in breast cancer. Extracellular vesicles in blood and breast fluid may have a great potential to detect and predict the presence of breast cancer, and extracellular vesicles modulation may emerge as a therapeutic approach in cancer therapy.

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Nano-Vesicle (Mis)Communication in Senescence-Related Pathologies

Cells ◽

10.3390/cells9091974 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1974

Author(s):

Sherin Saheera ◽

Ajay Godwin Potnuri ◽

Prasanna Krishnamurthy

Keyword(s):

Extracellular Vesicles ◽

Biological Fluids ◽

Critical Role ◽

Biological Information ◽

Multivesicular Bodies ◽

Apoptotic Bodies ◽

Signaling Crosstalk ◽

Progressive Decline ◽

Exosome Biogenesis ◽

And Function

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising of exosomes, apoptotic bodies, and microvesicles. Of the extracellular vesicles, exosomes are the most widely sorted and extensively explored for their contents and function. The size of the nanovesicular structures (exosomes) range from 30 to 140 nm and are present in various biological fluids such as saliva, plasma, urine etc. These cargo-laden extracellular vesicles arise from endosome-derived multivesicular bodies and are known to carry proteins and nucleic acids. Exosomes are involved in multiple physiological and pathological processes, including cellular senescence. Exosomes mediate signaling crosstalk and play a critical role in cell–cell communications. Exosomes have evolved as potential biomarkers for aging-related diseases. Aging, a physiological process, involves a progressive decline of function of organs with a loss of homeostasis and increasing probability of illness and death. The review focuses on the classic view of exosome biogenesis, biology, and age-associated changes. Owing to their ability to transport biological information among cells, the review also discusses the interplay of senescent cell-derived exosomes with the aging process, including the susceptibility of the aging population to COVID-19 infections.

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Apoptotic Bodies: Particular Extracellular Vesicles Involved in Intercellular Communication

Biology ◽

10.3390/biology9010021 ◽

2020 ◽

Vol 9 (1) ◽

pp. 21 ◽

Cited By ~ 13

Author(s):

Michela Battistelli ◽

Elisabetta Falcieri

Keyword(s):

Extracellular Vesicles ◽

Intercellular Communication ◽

Genetic Information ◽

Cell Communication ◽

Cell Types ◽

Apoptotic Bodies ◽

Species Barrier ◽

Physiological Conditions ◽

Different Types ◽

Different Cell Types

In the last decade, a new method of cell–cell communication mediated by membranous extracellular vesicles (EVs) has emerged. EVs, including exosomes, microvesicles, and apoptotic bodies (ApoBDs), represent a new and important topic, because they are a means of communication between cells and they can also be involved in removing cellular contents. EVs are characterized by differences in size, origin, and content and different types have different functions. They appear as membranous sacs released by a variety of cells, in different physiological and patho-physiological conditions. Intringuingly, exosomes and microvesicles are a potent source of genetic information carriers between different cell types both within a species and even across a species barrier. New, and therefore still relatively poorly known vesicles are apoptotic bodies, on which numerous in-depth studies are needed in order to understand their role and possible function. In this review we would like to analyze their morpho-functional characteristics.

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Extracellular Vesicles: From Biomarkers to Therapeutic Tools

Biology ◽

10.3390/biology9090258 ◽

2020 ◽

Vol 9 (9) ◽

pp. 258

Author(s):

Simona Bernardi ◽

Carolina Balbi

Keyword(s):

Extracellular Vesicles ◽

Intercellular Communication ◽

Cell Contact ◽

Apoptotic Bodies ◽

Therapeutic Tool ◽

The Status ◽

Direct Cell ◽

Therapeutic Tools ◽

Multicellular Organisms ◽

Target Cancer

Intercellular communication is an essential hallmark of multicellular organisms and can be mediated through direct cell–cell contact or transfer of secreted molecules. In the last two decades, a third mechanism for intercellular communication has emerged that involves intercellular transfer of extracellular vesicles (EVs). EVs are membranous vesicles of 30–5000 nm in size. Based on their dimension and biogenesis, EVs can be divided into different categories, such as microvesicles, apoptotic bodies, ectosomes, and exosomes. It has already been demonstrated that protein changes, expressed on the surfaces or in the content of these vesicles, may reflect the status of producing cells. For this reason, EVs, and exosomes in particular, are considered ideal biomarkers in several types of disease—from cancer diagnosis to heart rejection. This aspect opens different opportunities in EVs clinical application, considering the importance given to liquid biopsy in the recent years. Furthermore, extracellular vesicles can be natural or engineered carriers of cytoprotective or cytotoxic factors and applied, as a therapeutic tool, from regenerative medicine to target cancer therapy. This is of pivotal importance in the so called “era of the 4P medicine”. This Editorial focuses on recent findings pertaining to EVs in different medical areas, from biomarkers to therapeutic applications.

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