Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: June 28, 2022

Abstract Cancer is one of the leading causes death worldwide, and factors responsible for its progression need to be elucidated. Exosomes are structures with an average size 100 nm that can transport proteins, lipids, nucleic acids. This review focuses on role exosomes in cancer therapy. We discuss how able modulate components tumor microenvironment influence proliferation migration rates cells. also highlight that, depending their cargo, suppress or promote cell enhance reduce response radio- chemo-therapies. In addition, we describe trigger chronic inflammation lead immune evasion by focusing ability transfer non-coding RNAs between cells other molecular signaling pathways such as PTEN PI3K/Akt cancer. Subsequently, use carriers anti-tumor agents genetic tools control progression. then tumor-derived carcinogenesis. Finally, devote a section study diagnostic prognostic clinical courses important treatment patients. provides comprehensive understanding therapy, therapeutic value remodeling microenvironment. Graphical

Language: Английский

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Extracellular vesicles as tools and targets in therapy for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 5, 2024

Abstract Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers ubiquitously released from cells under normal pathological conditions. Human serum is a rich source of these EVs, though their isolation proteins non-EV lipid particles poses challenges. These transport various cellular components such as proteins, mRNAs, miRNAs, DNA, lipids across distances, influencing numerous physiological events, including those within tumor microenvironment (TME). Their pivotal roles in communication make EVs promising candidates for therapeutic agents, drug delivery systems, disease biomarkers. Especially cancer diagnostics, EV detection can pave way early identification offers potential diagnostic Moreover, subtypes emerging targeted tools, highlighting clinical significance. The need non-invasive biomarkers to monitor biological processes purposes remains unfulfilled. Tapping unique composition could unlock advanced avenues future. In this review, we discuss detail conditions, cancers (encompassing head neck, lung, gastric, breast, hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune renal diseases, emphasizing advancements molecular diagnostics delivery.

Language: Английский

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Ovarian cancer cell-secreted exosomal miR-205 promotes metastasis by inducing angiogenesis

Theranostics, Journal Year: 2019, Volume and Issue: 9(26), P. 8206 - 8220

Published: Jan. 1, 2019

Background: By providing oxygen, nutrients and metastatic conduits, tumour angiogenesis is essential for cancer metastasis. Cancer cell-secreted microRNAs can be packaged into exosomes are implicated in different aspects of angiogenesis. However, the underlying mechanisms incompletely understood. Methods: The GEPIA database situ hybridization assay were used to analyse expression miR-205 ovarian tissues. Immunohistochemistry was performed examine relationship between microvessel density. Expression circulating evaluated by RT-PCR GEO analysis. Co-culture exosome labelling experiments assess exosomal transfer from (OC) cells endothelial ECs. Exosome uptake assays employed define cellular pathways associated with endocytic miR-205. role further investigated vivo vitro. Western blotting rescue applied detect regulation PTEN-AKT pathway Results: up-regulated OC tissues, high progression patients. Moreover, highly enriched cancer-adjacent ECs, up-regulation correlated positively density Importantly, markedly serum patients, a level In addition, OC-derived secreted extracellular space efficiently transferred adjacent ECs an exosome-dependent manner, lipid raft-associated plays important regulating Exosomal significantly promoted vitro accelerated growth mouse model. Furthermore, we found that induces via pathway. Conclusion: These findings demonstrate mechanism which derived regulates implicate as potential therapeutic target OC.

Language: Английский

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Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: June 5, 2020

Abstract Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis their origination from the endosomal or plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer growth metastasis. EVs derived different status have been shown to distinct RNA profiles, comprising messenger RNAs non-coding (ncRNAs). Recently, ncRNAs attracted great interests in field EV-RNA research, growing numbers ranging microRNAs long investigated reveal specific functions underlying mechanisms tumor microenvironment premetastatic niches. Emerging evidence has indicated that EV-RNAs essential functional cargoes modulating hallmarks cancers reciprocal crosstalk within cells between stromal over short distance, thereby regulating initiation, development progression cancers. In this review, we discuss current findings regarding EV biogenesis, release interaction with target as well sorting, highlight biological roles molecular EV-ncRNAs biology.

Language: Английский

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Emerging Function and Clinical Values of Exosomal MicroRNAs in Cancer

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 16, P. 791 - 804

Published: May 15, 2019

Exosomes are a subset of membrane-bound extracellular vesicles with diameters ranging from 30 to 100 nm. enclose variety molecules, such as lipids, proteins, and non-coding RNAs. In the past decades, microRNAs (miRNAs) have attracted great attention in cancer research, they play an important role occurrence development cancer. Increasing evidence indicates that tumor cells communicate not only other but also present microenvironment via secretion transfer exosomal miRNAs. More importantly, miRNAs found serve signaling molecules regulate growth, angiogenesis, metastasis, sensitivity chemotherapy, immune evasion. Deregulated expression is early event carcinogenesis may reflect malignant characteristics Owing wide existence high stability body fluids, represent novel class non-invasive biomarkers for this review, we highlight recent advances on functional pathogenesis. 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Lung Cancer. 2009; 42-46Abstract (1020) demonstrating ideal summarize current knowledge progression. applications practice. generated both pathological fluids.31Brinton L.T. Sloane H.S. Kester Kelly K.A. Formation cancer.Cell. 72: 659-671Crossref (154) originate compartment.32Gruenberg van der Goot F.G. pathogen entry compartments.Nat. 2006; 7: 495-504Crossref (269) biogenesis involves two steps.33Kowal Tkach Biogenesis exosomes.Curr. 2014; 29: 116-125Crossref (1073) First, internalization leads formation endosomes (Figure 1). intraluminal (ILVs) then formed inward invagination membranes, resulting MVBs. During process, cytosolic sorted ILVs. Upon membrane, ILVs milieu. Some factors exosome biogenesis. sorting complexes required transport (ESCRTs) essential MVB biogenesis, which cargo coupled detachment ILVs.34Wollert Hurley Molecular ESCRT complexes.Nature. 464: 864-869Crossref (504) ESCRT-0 responsible assembly gathering cargoes. ESCRT-I -II harbor various membrane-binding sites, membrane. capable bud, cargoes confined. ESCRT-II recruits ESCRT-III subunits, vacuolar protein sorting-associated 20 (Vps20) eukaryotic sucrose non-fermenting 7 (Snf7), neck bud. complex directs scission cytoplasmic side Following scission, entrapped while ESCR-III persists outside remaining until it recycled. Moreover, accessory ALG-2-interacting X (ALIX) susceptibility gene 101 (TSG101), packaging ALIX encloses enter internalized vesicle formation.35Baietti M.F. Z. Mortier Melchior Degeest Geeraerts Ivarsson Depoortere Coomans Vermeiren et al.Syndecan-syntenin-ALIX regulates exosomes.Nat. 677-685Crossref (1022) complex, ILVs.36Hurley Odorizzi Get bus ALIX.Nat. 654-655Crossref (145) TSG101, component machinery, epidermal growth factor (EGF)-stimulated formation.37Razi Futter C.E. Distinct Tsg101 Hrs vesiculation.Mol. 3469-3483Crossref (191) Accordingly, depletion TSG101 suppress formation. Members Rab GTPase family (e.g., Rab27a Rab27b) mediate trafficking site membrane.38Bobrie Krumeich Reyal Recchi Moita L.F. Seabra Ostrowski supports exosome-dependent -independent modify progression.Cancer Res. 4920-4930Crossref (399) 39Ostrowski Carmo N.B. Fanget I. Savina C.F. Schauer Hume A.N. Freitas R.P. al.Rab27a Rab27b control different steps pathway.Nat. 19-30Crossref (1516) requires contractile machinery able draw opposing membranes together prior shearing connection releasing milieu.40Cocucci Racchetti Meldolesi Shedding microvesicles: artefacts no more.Trends 19: 43-51Abstract (1360) Soluble N-ethylmaleimide-sensitive attachment receptor (SNARE) facilitate membrane.41Südhof T.C. Rothman J.E. Membrane fusion: grappling SNARE SM proteins.Science. 323: 474-477Crossref (1404) represents focus investigation would enrich our underlying A incorporated exosomes, miRNAs, DNAs, RNAs, proteins. 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Yi Hudson R.S. Howe T.M. Petrocca Wallace T.A. C.G. Volinia al.Genomic messenger RNA reveals deregulated prostate cancer.Cancer 68: 6162-6170Crossref (594) miR-142-3p, miR-150, miR-451 were enriched parent preferentially packaged exosomes.51Guduric-Fuchs O'Connor Camp O'Neill C.L. Medina R.J. Simpson D.A. Selective vesicle-mediated export overlapping set types.BMC Genomics. 13: 357Crossref (363) Likewise, members let-7 more abundant derived gastric (GC) than those cells.52Ohshima Inoue Fujiwara Hatakeyama Kanto Watanabe Muramatsu Fukuda Ogura Yamaguchi Mochizuki Let-7 selectively environment metastatic line.PLoS ONE. 5: e13247Crossref (484) Remarkably, some miR-21, let-7f, miR-20b, miR-30e-3p) exhibited levels patients healthy controls.53Skog Würdinger Rijn Meijer D.H. Gainche Sena-Esteves Curry Jr., W.T. Carter B.S. Krichevsky Breakefield X.O. Glioblastoma microvesicles proteins tumour provide biomarkers.Nat. 1470-1476Crossref (3541) 54Silva García Zaballos Á. Provencio Lombardía Almonacid Domínguez Peña Diaz al.Vesicle-related nonsmall correlation survival.Eur. Respir. 617-623Crossref (219) adopt specific direct loading leading selective encapsulation cell-secreted exosomes. Four pathways proposed 2). neural sphingomyelinase 2 (nSMase2)-dependent pathway was guide nSMase2 first molecule exosomes.55Zhang Guo Yao Mi trafficking, sorting, function.Genomics Proteomics Bioinformatics. 17-24Crossref (1050) Overexpression caused increase abundance miRNAs.56Kosaka Iguchi Hagiwara Yoshioka Takeshita Ochiya Neutral angiogenic Chem. 288: 10849-10859Abstract (497) contrast, inhibition decreased second sumoylated heterogeneous nuclear ribonucleoprotein (hnRNP)-dependent pathway. Three hnRNP (hnRNPA2B1, hnRNPA1, hnRNPC) bound induced exosomes.57Villarroya-Beltri Gutiérrez-Vázquez Sánchez-Cabo Pérez-Hernández Vázquez Martin-Cofreces Martinez-Herrera D.J. Pascual-Montano Sánchez-Madrid Sumoylated hnRNPA2B1 controls motifs.Nat. Commun. 4: 2980Crossref (1124) Specially, controlled assortment recognizing GGAG motif part sequences. third depends end miRNA. sequence might contain signal contributed guiding incorporation exosomes.58Koppers-Lalic Hackenberg Bijnsdorp I.V. Eijndhoven M.A.J. Sadek Sie Zini Middeldorp Ylstra Menezes R.X. al.Nontemplated nucleotide additions distinguish composition exosomes.Cell Rep. 8: 1649-1658Abstract (371) last mediated miRNA-induced silencing (miRISC). primary miRISC co-localize MVBs.59Gibbings Ciaudo Erhardt Voinnet O. Multivesicular associate effector modulate activity.Nat. 1143-1149Crossref (787) blockade turnover lysosomes resulted accumulation miRISCs, suppression loss relieved miRNA-mediated silencing.60Lee Y.S. Pressman Andress A.P. White J.L. Cassidy Lubell Lim Cho I.S. al.Silencing linked trafficking.Nat. 1150-1156Crossref (270) It reported activation-dependent changes abundance.61Squadrito Baer Burdet Maderna Gilfillan G.D. Lyle Ibberson De Palma Endogenous acceptor cells.Cell 1432-1446Abstract (417) Artificially elevating benefited enrichment Argonaute (Ago2), RISC, implicated Knockout Ago2 could reduce miR-451.51Guduric-Fuchs Collectively, certain sequences favor uptake Nevertheless, remain unclear deserve further investigation. shown exert multifaceted effects progression, regulation angiogenesis domination host responses, manipulation chemoresistance, 3). Proliferation aspect commonly manifested cycle-related contributing metastasis. cancer-secreted proliferation targeting cycle-associated pathways. miR-200b transmitted colorectal (CRC) promoted recipient lowering p27 expression.62Zhang Xing promotes TGF-β1 exposure.Biomed. Pharmacother. 106: 1135-1143Crossref (2) miR-6869-5p depress CRC inhibit inflammatory (interleukin-6 [IL-6] necrosis alpha [TNF-α]) blocking Toll-like 4 (TLR4)/nuclear κB (NF-κB)-signaling pathway.63Yan Jin Duan Xu MicroRNA-6869-5p acts suppressor TLR4/NF-κB cancer.J. 233: 6660-6668Crossref Inhibition oncogenic miR-21 suppressed migration hepatocellular carcinoma (HCC) cells.64Liang He Miao Wu Gan Sphk2 RNAi nanoparticles downregulating microRNA.J. Control. Release. 286: 348-357Crossref (1) miR-9-3p restrained HCC directly fibroblast 5 (HBGF-5).65Tang Zhu Yang W.H. Xiong L.K. D.L. suppresses HBGF-5 biomarker carcinoma.Minerva 109: 15-23PubMed miR-1246, transferred non-malignant cells.66Li X.J. Ren Z.J. Tang Yu MiR-1246 Promotes Proliferation, Invasion Drug Resistance Targeting CCNG2 Breast Cancer.Cell. 44: 1741-1748Crossref (167) miR-1246 migration, resistance cyclin-G2 (CCNG2). miR-193a impeded cycle exerted inhibitory effect colon 1 (Caprin1).67Teng Hu Mu Samykutty Zhuang Deng Kumar Merchant al.MVP-mediated progression.Nat. 14448Crossref (260) orchestrate apoptotic cells. For instance, miR-128 reduced Bcl-2-associated (Bax) cells.68Wei Cui Shikonin Inhibits Cells Reducing Tumor-Derived Exosomes.Molecules. 21: 777Crossref (21) miR-373 repressed estrogen (ER) inhibited apoptosis cells.69Eichelser Stückrath Müller Milde-Langosch Wikman Pantel Schwarzenbach Increased serum circulating microRNA-373 receptor-negative patients.Oncotarget. 9650-9663Crossref adipose mesenchymal stem (hAMSC)-derived induce (OC) upregulating (Bax, caspase 3, 9) anti-apoptotic Bcl-2.70Reza A.M.M.T. Y.J. Yasuda exosomal-miRNAs anti-proliferation signalling A2780 SKOV-3 cells.Sci. 38498Crossref (31) miR-101 GC myeloid leukemia-1 (Mcl-1).71Imamura Komatsu Ichikawa Miyamae Okajima Ohashi Kiuchi Nishibeppu Kosuga Konishi al.Low cancer.Oncotarget. 106538-106550Crossref (9) epithelial-mesenchymal transition (EMT), vital process invasion characterized

Language: Английский

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Expression, regulation, and function of exosome‐derived miRNAs in cancer progression and therapy

The FASEB Journal, Journal Year: 2021, Volume and Issue: 35(10)

Published: Sept. 12, 2021

Exosomes are a novel class of intercellular signal modulators that contain wide range molecules and deliver information between cells tissues. MicroRNAs (miRNAs), type regulatory non-coding RNA, often incorporated into exosomes as signaling molecules. In this review, we discuss the expression exosomal miRNAs from diverse origins such tumor cells, solid tissue, biological fluids in various cancers (lung, breast, colorectal, liver, stomach, pancreatic). We address functions exosome-derived processes tumor-cell proliferation, angiogenesis, metastasis, chemoresistance microenvironment. particular, three oncogenic miRNAs, miR-21, miR-141, miR-451, which occur within exosomes, terms gene regulation communication. consider therapeutic miRNA-based nanoparticles, widely expressed tumors show promise drug therapy. The review assesses wide-ranging evidence for using markers molecular diagnosis. Further, use nanoparticle platforms to transport targeted treatment disease tumors.

Language: Английский

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RETRACTED ARTICLE: Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma

Angiogenesis, Journal Year: 2019, Volume and Issue: 22(3), P. 397 - 410

Published: April 15, 2019

Language: Английский

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Exosomal miRNAs in tumor microenvironment

Journal of Experimental & Clinical Cancer Research, Journal Year: 2020, Volume and Issue: 39(1)

Published: April 16, 2020

Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of cells, fibroblasts, endothelial and immune as well non-cellular components, such exosomes cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, proteins, lipids nucleic acids. carry biologically miRNAs to shuttle between TME, thereby affecting development. Tumor-derived exosomal induce matrix reprogramming creating a that conducive growth, metastasis, escape chemotherapy resistance. In this review, we updated role process TME reshaping.

Language: Английский

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Extracellular vesicles and particles impact the systemic landscape of cancer

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(18)

Published: Sept. 2, 2022

Language: Английский

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MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 17, 2022

MicroRNAs (miRNAs) are a class of short, single-stranded, noncoding RNAs, with length about 18–22 nucleotides. Extracellular vesicles (EVs) derived from cells and play vital role in the development diseases can be used as biomarkers for liquid biopsy, they carriers miRNA. Existing studies have found that most functions miRNA mainly realized through intercellular transmission EVs, which protect sort miRNAs. Meanwhile, detection sensitivity specificity EV-derived higher than those conventional serum biomarkers. In recent years, EVs been expected to become new marker biopsy. This review summarizes progress several aspects including sorting mechanisms, diagnostic value, technology isolation addition, study reviews challenges future research avenues field providing basis application miRNAs disease clinical diagnosis even point-of-care testing (POCT) platforms.

Language: Английский

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