M2 macrophage-derived exosomal miR-193b-3p promotes progression and glutamine uptake of pancreatic cancer by targeting TRIM62 DOI Creative Commons
Ke Zhang, Yujie Li,

Linjia Peng

и другие.

Biology Direct, Год журнала: 2023, Номер 18(1)

Опубликована: Янв. 11, 2023

Pancreatic cancer (PC) is a highly lethal malignancy that requires effective novel therapies. M2 macrophages are abundant in the PC microenvironment and promote progression. Exosomes emerging mediators of crosstalk between cells microenvironment. This study was conducted to explore role macrophage-derived exosomes PC.Exosomes derived from were extracted. miR-193b-3p TRIM62 overexpressed or silenced examine their function PC. Luminescence assays used investigate interaction TRIM62. Cell proliferation examined by EdU staining. Would healing transwell applied evaluate cell migration invasion. Co-immunoprecipitation assess c-Myc. Gene protein expressions analyzed quantitative RT-PCR immunoblotting, respectively.M2 exosomal promoted proliferation, migration, invasion, glutamine uptake SW1990 cells. Mechanism revealed target miR-193b-3p. inhibited promoting c-Myc ubiquitination. Our data also suggested expression negatively correlated with expression. High-expression predicts poor prognosis, whereas low-expression prognosis patients PC.M2 enhances targeting TRIM62, resulting decrease not only reveals mechanism underlying but suggests promising therapeutic for

Язык: Английский

Exosomes as a new frontier of cancer liquid biopsy DOI Creative Commons
Dan Yu,

Yixin Li,

Maoye Wang

и другие.

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

543

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

Enli Yang,

Xuan Wang, Zhiyuan Gong

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

315

Extracellular Vesicles in Cancer Immune Microenvironment and Cancer Immunotherapy DOI Creative Commons
Feng Xie, Xiaoxue Zhou,

Meiyu Fang

и другие.

Advanced Science, Год журнала: 2019, Номер 6(24)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

255

Emerging Function and Clinical Values of Exosomal MicroRNAs in Cancer DOI Creative Commons
Man Wang, Fei Yu, Han Ding

и другие.

Molecular Therapy — Nucleic Acids, Год журнала: 2019, Номер 16, С. 791 - 804

Опубликована: Май 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. We discuss potential clinical utility exosome-shuttled diagnosis treatment 30- 100-nm endosomal origin, comprising lipid bilayer bioactive nucleic acids, proteins.1Abak A. Abhari Rahimzadeh S. cancer: small vesicular transporters progression therapeutics.PeerJ. 2018; 6: e4763Crossref PubMed Scopus (6) Google Scholar released all cell types, including epithelial cells, cells.2Pap E. Pállinger Falus The membrane tumorigenesis.Crit. Rev. Oncol. Hematol. 2011; 79: 213-223Crossref (0) Scholar, 3van Niel G. Raposo Candalh C. Boussac M. Hershberg R. Cerf-Bensussan N. Heyman Intestinal secrete exosome-like vesicles.Gastroenterology. 2001; 121: 337-349Abstract Full Text PDF 4Blanchard Lankar D. Faure F. Regnault Dumont Hivroz TCR activation human T induces production exosomes bearing TCR/CD3/zeta complex.J. Immunol. 2002; 168: 3235-3241Crossref Notably, excessive amounts compared normal proliferating cells.5Kharaziha P. Ceder Li Q. Panaretakis T. 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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. 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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

Язык: Английский

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172

Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance DOI Creative Commons
Shujing Wang, Jingrui Wang, Zhiqiang Chen

и другие.

npj Precision Oncology, Год журнала: 2024, Номер 8(1)

Опубликована: Фев. 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,

Язык: Английский

Процитировано

148

Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 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.

Язык: Английский

Процитировано

145

The role of Exosomal miRNAs in cancer DOI Creative Commons
Chuanyun Li, Tong Zhou, Jing Chen

и другие.

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Янв. 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.

Язык: Английский

Процитировано

104

Extracellular vesicles: Emerging tools as therapeutic agent carriers DOI Creative Commons
Shan Liu,

Xue Wu,

Sutapa Chandra

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2022, Номер 12(10), С. 3822 - 3842

Опубликована: Май 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.

Язык: Английский

Процитировано

85

miRNA Biogenesis and Regulation of Diseases: An Updated Overview DOI

Anchal Vishnoi,

Sweta Rani

Methods in molecular biology, Год журнала: 2022, Номер unknown, С. 1 - 12

Опубликована: Ноя. 28, 2022

Язык: Английский

Процитировано

84

Renal cell carcinoma-derived exosomes deliver lncARSR to induce macrophage polarization and promote tumor progression via STAT3 pathway DOI Creative Commons
Wei Zhang, Xiaoxiao Zheng, Yisong Yu

и другие.

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(8), С. 3209 - 3222

Опубликована: Янв. 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.

Язык: Английский

Процитировано

70