Exosomes in cancer: small particle, big player

Journal of Hematology & Oncology, Год журнала: 2015, Номер 8(1)

Опубликована: Июль 9, 2015

Exosomes have emerged as a novel mode of intercellular communication. can shuttle bioactive molecules including proteins, DNA, mRNA, well non-coding RNAs from one cell to another, leading the exchange genetic information and reprogramming recipient cells. Increasing evidence suggests that tumor cells release excessive amount exosomes, which may influence initiation, growth, progression, metastasis, drug resistance. In addition, exosomes transfer message immune stromal cells, contributing escape surveillance formation niche. this review, we highlight recent advances in biology cancer communicasomes. We review multifaceted roles small secreted particles, communicating with other within microenvironment. Given are type specific, stable, accessible body fluids, provide promising biomarkers for diagnosis represent new targets therapy.

Язык: Английский

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Exosomal miRNAs as cancer biomarkers and therapeutic targets

Journal of Extracellular Vesicles, Год журнала: 2016, Номер 5(1)

Опубликована: Янв. 1, 2016

Intercommunication between cancer cells and with their surrounding distant environments is key to the survival, progression metastasis of tumour. Exosomes play a role in this communication process. MicroRNA (miRNA) expression frequently dysregulated tumour can be reflected by distinct exosomal miRNA (ex‐miRNA) profiles isolated from bodily fluids patients. Here, potential ex‐miRNA as biomarker therapeutic target critically analysed. are stable source but, despite number methods for exosome extraction quantification, suitability diagnostics clinical setting questionable. Furthermore, exosomally transferred miRNAs alter behaviour recipient stromal promote oncogenesis, highlighting cell cancer. However, our incomplete understanding biogenesis loading mechanisms means that strategies exosomes or limited not specific cells. Therefore, if employed novel non‐invasive diagnostic approaches cancer, two further advances necessary: isolate detect ex‐miRNA, better functions tumour‐cell communication.

Язык: Английский

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Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p

EBioMedicine, Год журнала: 2018, Номер 36, С. 209 - 220

Опубликована: Сен. 20, 2018

Cancer-associated fibroblasts (CAFs) play an important role in regulating tumor progression by transferring exosomes to neighboring cells. Our aim was clarify the of microRNA encapsulated derived from CAFs oral squamous cell carcinoma (OSCC).We examined expression profiles and donor-matched normal (NFs) patients with OSCC. We used confocal microscopy examine transportation exosomal miR-34a-5p between OSCC Next, luciferase reporter its mutant plasmids were confirm direct target gene miR-34a-5p. Phenotypic assays vivo growth experiments investigate functional significance miR-34a-5p.We found that CAF-derived significantly reduced, could transfer In xenograft experiments, overexpression inhibit tumorigenesis further revealed binds downstream AXL suppress proliferation metastasis. Stable ectopic cells overexpressing restored motility abolished miRNA. The miR-34a-5p/AXL axis promoted via AKT/GSK-3β/β-catenin signaling pathway, which induce epithelial-mesenchymal transition (EMT) promote cancer enhanced nuclear translocation β-catenin then induced transcriptional upregulation SNAIL, turn activated both MMP-2 MMP-9.The confers aggressiveness through AKT/GSK-3β/β-catenin/Snail cascade might represent a therapeutic for FUND: National Natural Science Foundation China.

Язык: Английский

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Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis

Cancer Letters, Год журнала: 2017, Номер 397, С. 33 - 42

Опубликована: Март 10, 2017

Язык: Английский

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Engineering Exosomes for Cancer Therapy

International Journal of Molecular Sciences, Год журнала: 2017, Номер 18(6), С. 1122 - 1122

Опубликована: Май 24, 2017

There remains an urgent need for novel therapeutic strategies to treat metastatic cancer, which results in over 8 million deaths annually worldwide. Following secretion, exosomes are naturally taken up by cells, and capable of the stable transfer drugs, microRNAs proteins. As knowledge biogenesis, release uptake continues evolve, thus also has interest these extracellular vesicles as potential tumor-targeted vehicles cancer therapy. The ability engineer exosome content migratory itinerary holds tremendous promise. Studies date have employed viral non-viral methods parent cells secrete modified exosomes, or alternatively, directly manipulate following secretion. majority studies demonstrated promising results, with decreased tumor cell invasion, migration proliferation, along enhanced immune response, death, sensitivity chemotherapy observed. outlined this review highlight exciting treatment. Successful implementation clinical setting will be dependent upon establishment rigorous standards manipulation, isolation, characterisation.

Язык: Английский

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Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell‐derived extracellular vesicles

Bioengineering & Translational Medicine, Год журнала: 2017, Номер 2(2), С. 170 - 179

Опубликована: Июнь 1, 2017

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have emerged as potential therapeutic agents for numerous applications. EVs offer advantages over cell-based therapies with regard to safety, stability and clearance profiles, however production potency limitations must be addressed enable eventual translation of EV-based approaches. Thus, we sought examine the role specific culture parameters on MSC EV bioactivity toward informing rational design scalable biomanufacturing. We report significantly reduced vascularization bioactivity, measured by an endothelial gap closure assay, increasing passage in trypsinization, especially beyond 4. further show that increased frequency collection yielded higher numbers from same initial number MSCs a 24 hr period. Finally, demonstrate decreased seeding density flasks resulted per other types. Overall, these studies highlight need careful consideration at laboratory scale large-scale biomanufacturing schemes.

Язык: Английский

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Exosomes and breast cancer drug resistance

Cell Death and Disease, Год журнала: 2020, Номер 11(11)

Опубликована: Ноя. 17, 2020

Abstract Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors tumor microenvironment, play an important role BC progression. With in-depth understanding heterogeneity, emerging exosomes drug has attracted extensive attention. The functional proteins or non-coding RNAs contained secreted from and stromal cells mediate by regulating efflux metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, microenvironmental remodeling. In this review, we summarize underlying associations between discuss unique biogenesis exosomes, change exosome cargo, pattern release response to treatment. Moreover, propose candidate biomarker predicting monitoring therapeutic potential target carrier reverse BC.

Язык: Английский

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Liquid Biopsy as a Tool for the Diagnosis, Treatment, and Monitoring of Breast Cancer

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(17), С. 9952 - 9952

Опубликована: Сен. 1, 2022

Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques guide breast therapy; however, these do not assess tumoral molecular heterogeneity. Personalized medicine aims overcome biological clinical complexities. Advances in computational analyses have enabled increasingly sensitive, specific, accurate application liquid biopsy. Such progress has ushered new era precision medicine, where objective personalized cancer, early screening, diagnosis prognosis, relapse detection, longitudinal monitoring, drug selection. Liquid can be defined as sampling components tumor cells that released from and/or metastatic deposits into blood, urine, feces, saliva, other substances. include circulating (CTCs), DNA (ctDNA) or RNA (ctRNA), platelets, exosomes. This review highlight role medicine.

Язык: Английский

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Exosomes in Cancer Liquid Biopsy: A Focus on Breast Cancer

Molecular Therapy — Nucleic Acids, Год журнала: 2017, Номер 10, С. 131 - 141

Опубликована: Дек. 1, 2017

The important challenge about cancer is diagnosis in primary stages and proper treatment. Although classical clinico-pathological features of the tumor have major prognostic value, advances treatment are indebted to discovery molecular biomarkers control pre-invasive state. Moreover, efficiency available therapeutic options highly diminished, chemotherapy still main due lack enough specific targets. Accordingly, finding new noninvasive for an clinical that not achieved yet. There current technologies screen, diagnose, prognose, treat cancer, but limitations these implements procedures undeniable. Liquid biopsy as a method has promising future field exosomes one recent areas drawn much attention. In this review, potential capability summarized with special focus on breast second cause mortality women all around world. It discusses reasons choose liquid studies related different found exosomes. exosome milk biofluid also discussed. At last, because choosing very challenging, summary techniques provided. Identification required early detection screening conquer cancer. Due heterogeneous characteristics most tumors genomic profiles, conventional biopsies cannot reflect whole nature or secondary (metastasis area). Each tissue provides small sample size fails heterogeneity, which essential procedure.1Esposito A. Criscitiello C. Locatelli M. Milano Curigliano G. solid tumors: understanding heterogeneity real time monitoring resistance targeted therapies.Pharmacol. Ther. 2016; 157: 120-124Crossref PubMed Scopus (72) Google Scholar, 2Gerlinger Rowan A.J. Horswell S. Math Larkin J. Endesfelder D. Gronroos E. Martinez P. Matthews N. Stewart et al.Intratumor branched evolution revealed by multiregion sequencing.N. Engl. Med. 2012; 366: 883-892Crossref (5730) Scholar detect therapy response, repeated cell sampling needed identify genetic changes during treatment, after surgery, accessible be monitored treatment.3Feller S.M. Lewitzky Hunting ultimate biopsy—let TEP dance begin.Cell Commun. Signal. 14: 24Crossref (17) low-cost detection, screening, investigating dynamics well risk relapses.4Izzotti Carozzo Pulliero Zhabayeva Ravetti J.L. Bersimbaev R. Extracellular microRNA biopsy: applicability prevention.Am. Cancer Res. 6: 1461-1493PubMed Isolation materials from bioliquids minimally invasive diagnose types cancers, some compartments cells (e.g., DNA, exosome, etc.) even segregate original bulk enter bloodstream any other bioliquid.5Perakis Speicher M.R. Emerging concepts biopsies.BMC 2017; 15: 75Crossref (167) Relative direct biopsies, easy-to-obtain makes them attractive alternative source application. Releasing biofluids could provide information tumors.3Feller 6Alix-Panabières Pantel K. 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Cell Biol. 88: 851-856Crossref (196) Scholar). exciting vast range biofluids, serum,15Manterola Guruceaga Gállego Pérez-Larraya González-Huarriz Jauregui Tejada Diez-Valle Segura V. Samprón Barrena al.A noncoding RNA GBM patient serum diagnostic tool.Neuro-oncol. 2014; 16: 520-527Crossref (260) normal malignant urine,16Bryzgunova O.E. Zaripov M.M. Skvortsova T.E. Lekchnov E.A. Grigor'eva A.E. Zaporozhchenko Morozkin E.S. Ryabchikova E.I. Yurchenko Y.B. Voitsitskiy V.E. Laktionov P.P. Comparative study urine healthy individuals patients.PLoS ONE. 11: e0157566Crossref (111) plasma, milk, saliva,17Lässer Alikhani V.S. Ekström Eldh Paredes P.T. Bossios Sjöstrand Gabrielsson Lötvall Valadi Human saliva, plasma contain RNA: uptake macrophages.J. Transl. 2011; 9Crossref (651) pleural effusions,18Gamperl Plattfaut Freund Quecke Theophil F. Gieseler effusions induce migration: inhibitory effect LMWH tinzaparin.Cell Int. 40: 1050-1061Crossref (30) bronchial lavage fluid,19Gregson A.L. Hoji Injean Poynter S.T. Briones Palchevskiy Weigt Shino M.Y. Derhovanessian Sayah al.Altered exosomal profiles bronchoalveolar lung transplants acute rejection.Am. Respir. Crit. Care 192: 1490-1503Crossref (48) ocular samples, tears,20Perkumas K.M. McKay B.S. Allingham R.R. Stamer W.D. Myocilin-associated human samples.Exp. Eye 2007; 84: 209-212Crossref (54) nasal fluid,21Lässer O'Neil S.E. Shelke G.V. Sihlbom Hansson S.F. Gho Y.S. Lundbäck B. nose immune trafficking harbour altered cargo chronic airway inflammation.J. 181Crossref (81) semen,22Madison M.N. Roller Okeoma semen contains potent anti-HIV-1 activity.Retrovirology. 102Crossref (99) synovial fluid,23Skriner Adolph Jungblut P.R. Burmester G.R. Association citrullinated exosomes.Arthritis Rheum. 2006; 54: 3809-3814Crossref (197) amniotic fluid, pregnancy-associated serum.24Keller Rupp Stoeck Runz Fogel Lugert Hager H.D. Abdel-Bakky M.S. Gutwein Altevogt CD24 marker secreted fluid.Kidney 72: 1095-1102Abstract (279) review advantages biopsy, especially exosome-based studies. Then diagnosis, (BC)16Bryzgunova investigated. Finally, scrutinized, concentrated methods laboratory works Traditional such fine needle aspiration, rely accessing cells25Wu Burstein D.E. Fine aspiration.Cancer Invest. 2004; 22: 620-628Crossref (65) relies subcellular particles cargos. Compared sources superiority aspects. First, compared apoptotic microvesicles, more homogeneous terms size,26Mathivanan Ji Simpson Exosomes: organelles communication.J. 73: 1907-1920Crossref (1768) cup-shaped appearance easily distinguishable through electron microscopy.27Luga Zhang Viloria-Petit A.M. Ogunjimi A.A. Inanlou Chiu Buchanan Hosein A.N. Basik Wrana mediate stromal mobilization autocrine Wnt-PCP signaling migration.Cell. 151: 1542-1556Abstract (951) Second, unlike circulating (CTCs) thought biomarkers,6Alix-Panabières many isolation characterization protocols developed use research therapy.28Lobb Becker Wen S.W. Wong C.S. Wiegmans A.P. Leimgruber Möller Optimized protocol culture supernatant plasma.J. Extracell. Vesicles. 4: 27031Crossref (952) commercial kits let us quickly efficiently isolate amount body liquid.29Kawakubo-Yasukochi Morioka Hayashi Y. Nishinakagawa Hazekawa Kawano Nakamura Nakashima SQUU-B line spreads its properties nonmetastatic clone SQUU-A same exosomes.J. Oral Biosci. 58: 33-38Crossref (5) Third, express HSP70 Alix, can applied separate vesicles.30Kosaka Iguchi Hagiwara Yoshioka Takeshita Neutral sphingomyelinase 2 (nSMase2)-dependent angiogenic microRNAs regulate metastasis.J. 288: 10849-10859Abstract (536) mirror presenting surface proteins31Gross J.C. Chaudhary Bartscherer Boutros Active Wnt exosomes.Nat. 1036-1045Crossref (680) target cells.32Chavez-Muñoz Morse Kilani Ghahary Primary keratinocytes externalize stratifin via Biochem. 104: 2165-2173Crossref (52) easy both cell-specific Fourth, stable circulation33Zhang X. Yuan Shi Wu Qian Xu cancer: particle, big player.J. Hematol. Oncol. 83Crossref (532) almost every fluid; therefore, they tools diseases BC. One BC antibody-targeted receptors carried exosomes, HER2,34Koga Matsumoto Akiyoshi Kubo Yamanaka Tasaki Kuroki Tanaka Katano Purification, biological significance tumor-derived exosomes.Anticancer 25: 3703-3707PubMed might trigger idea HER2 tool biopsy. Fifth, nucleic acid content practical investigation. Double-stranded DNA show mutational status cell.35Thakur B.K. Matei I. Huang Costa-Silva Zheng Hoshino Brazier Xiang al.Double-stranded novel biomarker detection.Cell 24: 766-769Crossref (1083) represent parental tumor-specific profiles,33Zhang architecture protects (miRNA) RNase catalytic function.36Cheng Sharples R.A. Scicluna B.J. Hill A.F. protective enriched miRNA intracellular cell-free blood.J. 3: 23743Crossref (544) Circular RNAs various than origin.37Dou Cha D.J. Jeppesen D.K. Weaver Prasad Levy Patton J.G. down-regulated transferred exosomes.Sci. Rep. 37982Crossref (245) Therefore, acids utilized find signatures patients cancer.38Alhasan A.H. Scott A.W. J.J. Feng Meeks Thaxton Mirkin C.A. high-risk cancer.Proc. Natl. Acad. Sci. USA. 113: 10655-10660Crossref (100) Databases ExoCarta39Keerthikumar Chisanga Ariyaratne Al Saffar Anand Zhao Samuel Pathan Jois Chilamkurti al.ExoCarta: web-based compendium cargo.J. Mol. 428: 688-692Crossref (776) Urinary Exosome Protein Database40Shao database: useful discovery.Adv. Exp. 845: 195-203Crossref (7) facilitate sharing data majority biomarker-based blood-derived Most body, release blood.41Hannafon B.N. Trigoso Y.D. Calloway C.L. Lum D.H. Welm Z.J. Blick K.E. Dooley W.C. Ding W.Q. Plasma indicative cancer.Breast 18: 90Crossref (346) concentration breast-specific (BSEs) seems decrease blood samples. However, fluids, full BSEs. Thus, reliable biomarkers. Hypothetically, BSEs tissue-specific bind specifically nanoengineering therapy. addition, collecting large scales purposes less serum. yield milk-derived (335 mg/L) purposes.42Munagala Aqil Jeyabalan Gupta R.C. Bovine drug delivery.Cancer Lett. 371: 48-61Crossref (506) regard, scientists traced using profile (including CXCL5, MIA, KLK6).43Larssen Wik Czarnewski Löf Ronquist K.G. Dubois Freyhult Gallant C.J. Oelrich al.Tracing cellular origin multiplex proximity extension assays.Mol. 502-511Abstract (55) showed drug-loaded bovine inhibit (MDA-MB-231 T47D) proliferation. concluded increased stability drug. regulatory system already demonstrated;44Corrado Raimondo Chiesi Ciccia De Leo Alessandro involved health disease: basic science applications.Int. 5338-5366Crossref (282) researchers presented anti-cancer impact NF-KB pathway H1299 cells.42Munagala Furthermore, 2016, Yassin al.45Yassin Abdel Hamid Amer Warda Farid O.A. Dromedary mammary transcriptome nano-vehicle: isolation, vesicular phospholipidomic characterizations.J. Adv. 7: 749-756Crossref (26) proposed camel potentially safe nanocarriers. Interestingly, high levels transforming growth factor-β2 (TGF-β2) promote epithelial-to-mesenchymal transition (EMT) MCF7 MCF10A cells. Hence, secretion TGF-β2 increase BC.46Qin Tsukasaki Dasgupta Mukhopadhyay Ikebe Sauter E.R. EMT.Clin. 4517-4524Crossref (106) opposite case, decreased viability vitro.47Reinhardt T.A. Lippolis J.D. Nonnecke Sacco R.E. proteome.J. 75: 1486-1492Crossref (170) under digestive acidic condition it ideal oral Loading paclitaxel (PTX) raised efficacy reduced systemic toxicity free PTX animal model cancer.48Agrawal A.K. Spencer W.A. Beck Gachuki Alhakeem Oben Munagala Bondada Milk-derived delivery paclitaxel.Nanomedicine (Lond.). 13: 1627-1636Crossref (281) A assessed capacity optimize curcumin mentioned proved encapsulated had higher solubility hydrophilic solutions, elevated Exosomal was conditions, endocytosis intestinal vitro.49Vashisht Rani Onteru S.K. Singh Curcumin resists digestion possesses enhanced permeability vitro.Appl. Biotechnol. 183: 993-1007Crossref conclusion, cost-effective carriers suitable Further investigation discover delivery. Similar tumor-related exert multiple functions growth, metastasis, chemoresistance. components (DNA, RNA, proteins) influence escape, invasion, angiogenesis.50Khan Jutzy J.M.S. Aspe J.R. Valenzuela Malyn M.A. Park J.S. Turay Wall N.R. application membrane therapy.in: Gali-Muhtasib Advances Therapy. InTech, 2011: 21-52Google Existence miRNAs malignancies. Triple-negative (TNBC) produce containing certain (Figure 1), result transformation. comparison pack neutral miRNAs.51Palma Yaddanapudi S.C. Pigati Havens Jeong Weiner G.A. Weimer Stern Hastings M.L. Duelli D.M. MicroRNAs exported customized particles.Nucleic Acids 9125-9138Crossref (176) Several investigations correlation between (miR-195,52Heneghan H.M. Miller Kelly Newell Kerin M.J. Systemic miRNA-195 differentiates malignancies detecting stage disease.Oncologist. 673-682Crossref (253) miR-21,53Asaga Kuo Nguyen Terpenning Giuliano Hoon D.S. Direct assay microRNA-21 concentrations advanced 57: 84-91Crossref (385) miR-484/19154Hu Z. Dong Wang L.E. Ma Liu Tang Chen Dai Wei Q. al.Serum risk: miR-484/191 endogenous controls.Carcinogenesis. 828-834Crossref (175) Scholar) tumorigenesis pathological stages. Hannafon al.41Hannafon indicated miR-21 miR-1246 those interestingly, Palma al.51Palma classified depending content. Analyzing five sequencing (RNA-seq) technique associated subtypes miRNAs.55Dhahbi J.M. Spindler S.R. Atamna Boffelli Martin D.I. Deep patterns 5′tRNA half YRNA fragment expression cancer.Biomark. Cancer. 37-47Crossref Fiskaa al.56Fiskaa Knutsen Nikolaisen Jørgensen Johansen S.D. Perander Seternes O.M. Distinct lines.PLoS e0161824Crossref (25) nine lines each non-BC lines. Based abundant focused role BC, al.57Park K.-h. Yong -Y.-r. Kang H.-j. Kim G.-h. D.-H. Lee M.-y. Composition kit diagnosing polynucleotide within vesicle, same.U.S. Patent. December (20170145519)Google designed kit. This equipment measures 10 aggregation indicates directs samples.57Park To sum up, bioliquid staging As miRNAs, differentially expressed extracted For example, CD24, likely late-stage biomarker,58van't Veer L.J. de Vijver He Hart Mao Peterse H.L. der Kooy Marton Witteveen A.T. al.Gene predicts outcome cancer.Nature. 2002; 415: 530-536Crossref (7763) exists seral exosomes.59Rupp Keller Brase Ehehalt Moldenhauer Marmé Sültmann Loss EpCAM proteolytic cleavage.Gynecol. 122: 437-446Abstract (208) 2005, Ryan al.60Ryan O'Donovan Browne O'Shea Crown A.D. McDermott O'Higgins Duffy Expression survivin splice variants survivin-2B survivin-DeltaEx3 cancer.Br. 92: (85) tissues apoptosis Khan al.61Khan McGregor D.W. Neidigh Survivin exosomes.Apoptosis. 1-12Crossref (202) considered packed Then, anti-apoptotic

Язык: Английский

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Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression

Tumor Biology, Год журнала: 2016, Номер 37(9), С. 12169 - 12180

Опубликована: Май 25, 2016

Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cells derived exosomes contribute to progression through the modulation of tumor microenvironment. However, effects from gastric on macrophages not well understood. In this study, we investigated biological role in activation macrophages. We demonstrated activated express increased levels proinflammatory factors, which turn promoted cell proliferation migration. addition, remarkably upregulated phosphorylation NF-κB Inhibiting reversed upregulation factors blocked their promoting Moreover, found could also activate human peripheral blood monocytes NF-κB. conclusion, our results suggest stimulate pathway promote progression, provides a potential therapeutic approach for interfering with interaction between

Язык: Английский

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