Exosomes as a new frontier of cancer liquid biopsy

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 18, 2022

Abstract Liquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged a revolutionary strategy for cancer diagnosis prognosis prediction. Exosomes are subset of extracellular vesicles (EVs) that shuttle molecular cargoes from donor cells to recipient play crucial role in mediating intercellular communication. Increasing studies suggest exosomes have great promise serve novel biomarkers liquid since large quantities enriched body fluids involved numerous physiological pathological processes. However, the further clinical application been greatly restrained lack high-quality separation component analysis methods. This review aims provide comprehensive overview on conventional technologies exosome isolation, characterization content detection. Additionally, roles serving potential biopsy diagnosis, treatment monitoring, prediction summarized. Finally, prospects challenges applying exosome-based precision medicine evaluated.

Language: Английский

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Exosome-mediated metabolic reprogramming: the emerging role in tumor microenvironment remodeling and its influence on cancer progression

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Oct. 19, 2020

Abstract Metabolic reprogramming is reported to be one of the hallmarks cancer, which an adaptive mechanism by fast-growing cancer cells adapt their increasing energy demands. Recently, extracellular vesicles (EVs) known as exosomes have been recognized crucial signaling mediators in regulating tumor microenvironment (TME). Meanwhile, TME a highly heterogeneous ecosystem incorporating cells, fibroblasts, adipocytes, endothelial mesenchymal stem and matrix. Accumulated evidence indicates that may transfer biologically functional molecules recipient facilitate progression, angiogenesis, metastasis, drug resistance, immunosuppression metabolism surrounding stromal cells. In this review, we present role underlying how exacerbate development through metabolic reprogramming. addition, will also discuss potential targeting process biomarkers for diagnosis prognosis, exosomes-mediated targets therapy. Furthermore, better understanding link between reprogramming, impact on would provide novel insights prevention treatment future.

Language: Английский

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Extracellular Vesicles in Cancer Immune Microenvironment and Cancer Immunotherapy

Advanced Science, Journal Year: 2019, Volume and Issue: 6(24)

Published: Oct. 23, 2019

Abstract Extracellular vesicles (EVs) are secreted by almost all cells. They contain proteins, lipids, and nucleic acids which delivered from the parent cells to recipient Thereby, they function as mediators of intercellular communication molecular transfer. Recent evidences suggest that exosomes, a small subset EVs, involved in numerous physiological pathological processes play essential roles remodeling tumor immune microenvironment even before occurrence metastasis cancer. Exosomes derived host mediate their mutual regulation locally or remotely, thereby determining responsiveness cancer therapies. As such, tumor‐derived circulating exosomes considered noninvasive biomarkers for early detection diagnosis tumor. Exosome‐based therapies also emerging cutting‐edge promising strategies could be applied suppress progression enhance anti‐tumor immunity. Herein, current understanding key modulating responses, well potential therapeutic applications outlined. The limitations studies presented directions future research described.

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. Among these compositions, substantial owing regulatory expression. ncRNAs approximately 19–24 nt length.42Chen Secreted new communication.Trends 22: 125-132Abstract (573) protein-coding level.43Bartel D.P. MicroRNAs: genomics, mechanism, function.Cell. 116: 281-297Abstract (28659) 44Ambros functions animal microRNAs.Nature. 431: 350-355Crossref (8837) 45Kim Siomi animals.Nat. 126-139Crossref (2504) constitute complicated networks fine-tuning biological death.46Miska E.A. How division, differentiation death.Curr. Genet. 563-568Crossref (701) 47Hwang H.W. Mendell J.T. death, tumorigenesis.Br. 94: 776-780Crossref (941) miRNA dysregulation associated progression.48Lee J.W. Choi C.H. Park Y.A. S.J. Hwang S.Y. W.Y. T.J. B.G. Bae D.S. Altered cervical carcinomas.Clin. 2535-2542Crossref (279) 49Tahiri Leivonen S.K. Lüders Steinfeld Ragle Aure Geisler Mäkelä Nord Riis M.L. Yakhini al.Deregulation cancer-related common benign tumors.Carcinogenesis. 35: 76-85Crossref (97) 50Ambs Prueitt R.L. 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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Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 10, 2024

Abstract Tumor drug resistance emerges from the interaction of two critical factors: tumor cellular heterogeneity and immunosuppressive nature microenvironment (TME). Tumor-associated macrophages (TAMs) constitute essential components TME. M2-like TAMs are in facilitating metastasis as well augmenting tumors. This review encapsulates mechanisms that use to promote resistance. We also describe emerging therapeutic strategies currently targeting combination with other antitumor drugs, some still undergoing clinical trial evaluation. Furthermore, we summarize analyze various existing approaches for developing novel drugs target overcome resistance, highlighting how can effectively stop growth, metastasis,

Language: Английский

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Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

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

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

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The role of Exosomal miRNAs in cancer

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Jan. 3, 2022

Exosomal miRNAs have attracted much attention due to their critical role in regulating genes and the altered expression of virtually all cancers affecting humans (Sun et al. Mol Cancer 17(1):14, 2018). modulate processes that interfere with cancer immunity microenvironment, are significantly involved tumor growth, invasion, metastasis, angiogenesis drug resistance. Fully investigating detailed mechanism occurrence development various could help not only treatment but also prevention malignant diseases. The current review highlighted recently published advances regarding cancer-derived exosomes, e.g., sorting delivery mechanisms for RNAs. cell-to-cell communication, impacting angiogenesis, metastasis multiple biological features, were discussed. Finally, potential exosomal as diagnostic prognostic molecular markers was summarized, well usefulness detecting resistance therapeutic agents.

Language: Английский

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Extracellular vesicles: Emerging tools as therapeutic agent carriers

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(10), P. 3822 - 3842

Published: May 11, 2022

Extracellular vesicles (EVs) are secreted by both eukaryotes and prokaryotes, present in all biological fluids of vertebrates, where they transfer DNA, RNA, proteins, lipids, metabolites from donor to recipient cells cell-to-cell communication. Some EV components can also indicate the type status their parent serve as diagnostic targets for liquid biopsy. EVs natively carry or be modified contain therapeutic agents (e.g., nucleic acids, polysaccharides, small molecules) physical, chemical, bioengineering strategies. Due excellent biocompatibility stability, ideal nanocarriers bioactive ingredients induce signal transduction, immunoregulation, other effects, which targeted specific cell types. Herein, we review classification, intercellular communication, isolation, characterization strategies apply therapeutics. This focuses on recent advances applications carriers vitro research towards vivo animal models early clinical applications, using representative examples fields cancer chemotherapeutic drug, vaccine, infectious disease vaccines, regenerative medicine gene therapy. Finally, discuss current challenges therapeutics future development.

Language: Английский

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miRNA Biogenesis and Regulation of Diseases: An Updated Overview

Methods in molecular biology, Journal Year: 2022, Volume and Issue: unknown, P. 1 - 12

Published: Nov. 28, 2022

Language: Английский

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Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(8), P. 3209 - 3222

Published: Jan. 1, 2022

Tumor-derived exosomes play a pivotal role in regulating tumor progression by mediating crosstalk between cells and immune such as macrophages within the microenvironment. Macrophages can adopt two distinct polarization statuses switch M1 or M2 activation phenotypes response to different external stimuli. However, of derived macrophage phenotypic development have not been elucidated renal cell carcinoma (RCC). Here we found that high infiltration was associated with worse prognosis RCC patients, therefore propose our hypothesis might directly influence thus promote progression. Both cell-based vitro models orthotopic transplantation vivo were constructed ELISA, flow cytometry, functional studies performed investigate whether how RCC-derived regulate growth. The results these polarization, cytokine release, phagocytosis, angiogenesis, development. Further study revealed amount recently discovered lncRNA called lncARSR exosomes. Overexpression induced changes promoted growth vivo, while knockdown siRNA disrupted exosomes-mediated polarization. LncARSR interacts miR-34/miR- 449 increase STAT3 expression mediate cells. Together, facilitate through inducing via transferring lncARSR, suggesting exosomes, are potential therapeutic targets for treatment RCC.

Language: Английский

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