Extracellular vesicles in urological malignancies: an update.
Journal
Nature reviews. Urology
ISSN: 1759-4820
Titre abrégé: Nat Rev Urol
Pays: England
ID NLM: 101500082
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
accepted:
07
11
2019
pubmed:
13
12
2019
medline:
6
2
2020
entrez:
13
12
2019
Statut:
ppublish
Résumé
Extracellular vesicles (EVs) have an essential functional role in local tumour progression, metastatic spread and the emergence of drug resistance in bladder, kidney and prostate cancer. Thus, EVs could be diagnostic, prognostic and predictive biomarkers for these malignancies. Virtually all biomolecules (including DNA, mRNA, microRNA, long non-coding RNA, proteins and lipids) packaged into EVs have been tested as biomarkers in blood and urine samples. The results are very heterogeneous, but promising biomarker candidates have been identified. Differing methods of EV isolation, characterization and analysis of their content have been used owing to a lack of international consensus; hence, comparing study results is challenging. Furthermore, validation of potential biomarkers in independent cohorts or prospective trials has rarely been performed. Future efforts to establish EV-derived biomarkers need to adequately address these points. In addition, emerging technologies such as mass spectroscopy and chip-based approaches can identify surface markers specific for cancer-associated EVs and will enable specific separation from blood and urine EVs, which probably will improve their performance as biomarkers. Moreover, EVs could be harnessed as therapeutic drug delivery vehicles for precise and effective anticancer therapy.
Identifiants
pubmed: 31827264
doi: 10.1038/s41585-019-0261-8
pii: 10.1038/s41585-019-0261-8
doi:
Substances chimiques
Biomarkers
0
MicroRNAs
0
RNA, Messenger
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
11-27Commentaires et corrections
Type : ErratumIn
Références
Thery, C. et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 7, 1535750 (2018).
pubmed: 30637094
pmcid: 6322352
Akers, J. C., Gonda, D., Kim, R., Carter, B. S. & Chen, C. C. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neurooncol. 113, 1–11 (2013).
pubmed: 23456661
pmcid: 5533094
Hessvik, N. P. & Llorente, A. Current knowledge on exosome biogenesis and release. Cell Mol. Life Sci. 75, 193–208 (2018).
pubmed: 28733901
Duijvesz, D., Luider, T., Bangma, C. H. & Jenster, G. Exosomes as biomarker treasure chests for prostate cancer. Eur. Urol. 59, 823–831 (2011).
pubmed: 21196075
van der Pol, E., Boing, A. N., Gool, E. L. & Nieuwland, R. Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles. J. Thromb. Haemost. 14, 48–56 (2016).
pubmed: 26564379
Kerr, J. F., Wyllie, A. H. & Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239–257 (1972).
pubmed: 4561027
pmcid: 2008650
Atkin-Smith, G. K. et al. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat. Commun. 6, 7439 (2015).
pubmed: 26074490
Hauser, P., Wang, S. & Didenko, V. V. Apoptotic bodies: selective detection in extracellular vesicles. Methods Mol. Biol. 1554, 193–200 (2017).
pubmed: 28185192
Stridsberg, M., Fabiani, R., Lukinius, A. & Ronquist, G. Prostasomes are neuroendocrine-like vesicles in human semen. Prostate 29, 287–295 (1996).
pubmed: 8899001
Carlsson, L. et al. Characteristics of human prostasomes isolated from three different sources. Prostate 54, 322–330 (2003).
pubmed: 12539232
Aalberts, M., Stout, T. A. & Stoorvogel, W. Prostasomes: extracellular vesicles from the prostate. Reproduction 147, R1–R14 (2014).
pubmed: 24149515
Zijlstra, C. & Stoorvogel, W. Prostasomes as a source of diagnostic biomarkers for prostate cancer. J. Clin. Invest. 126, 1144–1151 (2016).
pubmed: 27035806
pmcid: 4811138
Gould, S. J. & Raposo, G. As we wait: coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles 2, 20389 (2013).
Mulcahy, L. A., Pink, R. C. & Carter, D. R. Routes and mechanisms of extracellular vesicle uptake. J. Extracell. Vesicles 3, 24641 (2014).
Abels, E. R. & Breakefield, X. O. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell. Mol. Neurobiol. 36, 301–312 (2016).
pubmed: 27053351
pmcid: 5546313
O'Driscoll, L. Expanding on exosomes and ectosomes in cancer. N Engl. J. Med. 372, 2359–2362 (2015).
pubmed: 26061842
Junker, K., Heinzelmann, J., Beckham, C., Ochiya, T. & Jenster, G. Extracellular vesicles and their role in urologic malignancies. Eur. Urol. 70, 323–331 (2016).
pubmed: 26924769
Nawaz, M. et al. The emerging role of extracellular vesicles as biomarkers for urogenital cancers. Nat. Rev. Urol. 11, 688–701 (2014).
pubmed: 25403245
Tkach, M. & Thery, C. Communication by extracellular vesicles: where we are and where we need to go. Cell 164, 1226–1232 (2016).
pubmed: 26967288
Kosaka, N., Yoshioka, Y., Fujita, Y. & Ochiya, T. Versatile roles of extracellular vesicles in cancer. J. Clin. Invest. 126, 1163–1172 (2016).
pubmed: 26974161
pmcid: 4811151
Madeo, M. et al. Cancer exosomes induce tumor innervation. Nat. Commun. 9, 4284 (2018).
pubmed: 30327461
pmcid: 6191452
Ringuette Goulet, C. et al. Exosomes induce fibroblast differentiation into cancer-associated fibroblasts through TGFbeta signaling. Mol. Cancer Res. 16, 1196–1204 (2018).
pubmed: 29636362
Hoshino, A. et al. Tumour exosome integrins determine organotropic metastasis. Nature 527, 329–335 (2015).
pubmed: 26524530
pmcid: 4788391
Zhang, L. et al. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 527, 100–104 (2015).
pubmed: 26479035
pmcid: 4819404
Roccaro, A. M. et al. BM mesenchymal stromal cell-derived exosomes facilitate multiple myeloma progression. J. Clin. Invest. 123, 1542–1555 (2013).
pubmed: 23454749
pmcid: 3613927
Ono, M. et al. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci. Signal. 7, ra63 (2014).
pubmed: 24985346
Zhao, H. et al. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. eLife 5, e10250 (2016).
pubmed: 26920219
pmcid: 4841778
Lobb, R. J. et al. Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance. Int. J. Cancer 141, 614–620 (2017).
pubmed: 28445609
Qu, L. et al. Exosome-transmitted lncARSR promotes sunitinib resistance in renal cancer by acting as a competing endogenous RNA. Cancer Cell 29, 653–668 (2016).
pubmed: 27117758
Tang, Y. T. et al. Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum. Int. J. Mol. Med. 40, 834–844 (2017).
pubmed: 28737826
pmcid: 5548045
Ding, M. et al. Comparison of commercial exosome isolation kits for circulating exosomal microRNA profiling. Anal. Bioanal. Chem. 410, 3805–3814 (2018).
pubmed: 29671027
Chiriaco, M. S. et al. Lab-on-chip for exosomes and microvesicles detection and characterization. Sensors 18, E3175 (2018).
pubmed: 30241303
Sharma, S., LeClaire, M. & Gimzewski, J. K. Ascent of atomic force microscopy as a nanoanalytical tool for exosomes and other extracellular vesicles. Nanotechnology 29, 132001 (2018).
pubmed: 29376505
Grasso, L. et al. Molecular screening of cancer-derived exosomes by surface plasmon resonance spectroscopy. Anal. Bioanal. Chem. 407, 5425–5432 (2015).
pubmed: 25925862
pmcid: 4477949
Padda, R. S. et al. Nanoscale flow cytometry to distinguish subpopulations of prostate extracellular vesicles in patient plasma. Prostate 79, 592–603 (2019).
pubmed: 30680751
Morales-Kastresana, A. et al. Labeling extracellular vesicles for nanoscale flow cytometry. Sci. Rep. 7, 1878 (2017).
pubmed: 28500324
pmcid: 5431945
Jimenez, L. et al. Quantitative proteomic analysis of small and large extracellular vesicles (EVs) reveals enrichment of adhesion proteins in small EVs. J. Proteome Res. 18, 947–959 (2019).
pubmed: 30608700
pmcid: 6411421
Kreimer, S. et al. Mass-spectrometry-based molecular characterization of extracellular vesicles: lipidomics and proteomics. J. Proteome Res. 14, 2367–2384 (2015).
pubmed: 25927954
McGranahan, N. & Swanton, C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 27, 15–26 (2015).
pubmed: 25584892
Corcoran, R. B. & Chabner, B. A. Application of cell-free DNA analysis to cancer treatment. N. Engl. J. Med. 379, 1754–1765 (2018).
pubmed: 30380390
Gorin, M. A. et al. Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer. Nat. Rev. Urol. 14, 90–97 (2017).
pubmed: 27872478
Hille, C. & Pantel, K. Prostate cancer: circulating tumour cells in prostate cancer. Nat. Rev. Urol. 15, 265–266 (2018).
pubmed: 29508846
Werner, S., Keller, L. & Pantel, K. Epithelial keratins: biology and implications as diagnostic markers for liquid biopsies. Mol. Aspects Med. https://doi.org/10.1016/j.mam.2019.09.001 (2019).
Mader, S. & Pantel, K. Liquid biopsy: current status and future perspectives. Oncol. Res. Treat. 40, 404–408 (2017).
pubmed: 28693023
Volik, S., Alcaide, M., Morin, R. D. & Collins, C. Cell-free DNA (cfDNA): clinical significance and utility in cancer shaped by emerging technologies. Mol. Cancer Res. 14, 898–908 (2016).
pubmed: 27422709
Arroyo, J. D. et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl Acad. Sci. USA 108, 5003–5008 (2011).
pubmed: 21383194
pmcid: 3064324
Lotan, Y. & Roehrborn, C. G. Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta-analyses. Urology 61, 109–118 (2003).
pubmed: 12559279
Schmitz-Drager, B. J. et al. Molecular markers for bladder cancer screening, early diagnosis, and surveillance: the WHO/ICUD consensus. Urol. Int. 94, 1–24 (2015).
pubmed: 25501325
Mowatt, G. et al. Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer. Health Technol. Assess. 14, 1–331 (2010).
pubmed: 20557810
Armstrong, D. A., Green, B. B., Seigne, J. D., Schned, A. R. & Marsit, C. J. MicroRNA molecular profiling from matched tumor and bio-fluids in bladder cancer. Mol. Cancer 14, 194 (2015).
pubmed: 26576778
pmcid: 4650939
Baumgart, S. et al. Invasion-associated miRNAs S as possible diagnostic biomarkers of muscle invasive bladder cancer in tumor tissues and urinary exosomes. J. Urol. 199, E1038 (2018).
Andreu, Z. et al. Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression. Eur. J. Pharm. Sci. 98, 70–79 (2017).
pubmed: 27751843
De Long, J. et al. A non-invasive miRNA based assay to detect bladder cancer in cell-free urine. Am. J. Transl. Res. 7, 2500–250 (2015).
pubmed: 26807194
pmcid: 4697726
Royo, F. et al. Comparative miRNA analysis of urine extracellular vesicles isolated through five different methods. Cancers 8, E112 (2016).
pubmed: 27973407
Berrondo, C. et al. Expression of the long non-coding RNA HOTAIR correlates with disease progression in bladder cancer and is contained in bladder cancer patient urinary exosomes. PLOS ONE 11, e0147236 (2016).
pubmed: 26800519
pmcid: 4723257
Sanger, H. L., Klotz, G., Riesner, D., Gross, H. J. & Kleinschmidt, A. K. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc. Natl Acad. Sci. USA 73, 3852–3856 (1976).
pubmed: 1069269
pmcid: 431239
Chen, X. et al. PRMT5 circular RNA promotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition. Clin. Cancer Res. 24, 6319–6330 (2018).
pubmed: 30305293
Katsuda, T., Kosaka, N. & Ochiya, T. The roles of extracellular vesicles in cancer biology: toward the development of novel cancer biomarkers. Proteomics 14, 412–425 (2014).
pubmed: 24339442
Murakami, T. et al. Bladder cancer detection by urinary extracellular vesicle mRNA analysis. Oncotarget 9, 32810–32821 (2018).
pubmed: 30214686
pmcid: 6132352
Afsharpad, M. et al. Cancer-testis antigens as new candidate diagnostic biomarkers for transitional cell carcinoma of bladder. Pathol. Oncol. Res. 25, (191–199 (2019).
Esfandiary, A. & Ghafouri-Fard, S. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy. Immunotherapy 7, 411–439 (2015).
pubmed: 25917631
Yazarlou, F. et al. Urine exosome gene expression of cancer-testis antigens for prediction of bladder carcinoma. Cancer Manag. Res. 10, 5373–5381 (2018).
pubmed: 30464633
pmcid: 6225912
Lee, J. et al. Altered proteome of extracellular vesicles derived from bladder cancer patients urine. Mol. Cell 41, 179–187 (2018).
Silvers, C. R., Miyamoto, H., Messing, E. M., Netto, G. J. & Lee, Y. F. Characterization of urinary extracellular vesicle proteins in muscle-invasive bladder cancer. Oncotarget 8, 91199–91208 (2017).
pubmed: 29207636
pmcid: 5710916
Lin, S. Y. et al. Proteome profiling of urinary exosomes identifies alpha 1-antitrypsin and H2B1K as diagnostic and prognostic biomarkers for urothelial carcinoma. Sci. Rep. 6, 34446 (2016).
pubmed: 27686150
pmcid: 5043375
Silvers, C. R. et al. Identification of extracellular vesicle-borne periostin as a feature of muscle-invasive bladder cancer. Oncotarget 7, 23335–23345 (2016).
pubmed: 26981774
pmcid: 5029630
Zhang, S. et al. Evaluation of serum exosomal lncRNA-based biomarker panel for diagnosis and recurrence prediction of bladder cancer. J. Cell. Mol. Med. 23, 1396–1405 (2018).
pubmed: 30467945
pmcid: 6349164
Xue, M. et al. Hypoxic exosomes facilitate bladder tumor growth and development through transferring long non-coding RNA-UCA1. Mol. Cancer 16, 143 (2017).
pubmed: 28841829
pmcid: 5574139
Marconi, L. et al. Systematic review and meta-analysis of diagnostic accuracy of percutaneous renal tumour biopsy. Eur. Urol. 69, 660–673 (2016).
pubmed: 26323946
Zhang, W. et al. MicroRNAs in serum exosomes as potential biomarkers in clear-cell renal cell carcinoma. Eur. Urol. Focus 4, 412–419 (2018).
pubmed: 28753793
Zimpfer, A. et al. Prognostic and diagnostic implications of epithelial cell adhesion/activating molecule (EpCAM) expression in renal tumours: a retrospective clinicopathological study of 948 cases using tissue microarrays. BJU Int. 114, 296–302 (2014).
pubmed: 24215118
Wang, X. et al. Serum exosomal miR-210 as a potential biomarker for clear cell renal cell carcinoma. J. Cell. Biochem. https://doi.org/10.1002/jcb.27347 (2018).
Liu, H. et al. Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell renal cell carcinoma. BMC Syst. Biol. 4, 51 (2010).
pubmed: 20420713
pmcid: 2876063
Fujii, N. et al. Extracellular miR-224 as a prognostic marker for clear cell renal cell carcinoma. Oncotarget 8, 109877–109888 (2017).
pubmed: 29299115
pmcid: 5746350
Du, M. J. et al. Plasma exosomal miRNAs-based prognosis in metastatic kidney cancer. Oncotarget 8, 63703–63714 (2017).
pubmed: 28969022
pmcid: 5609954
Butz, H. et al. Exosomal microRNAs are diagnostic biomarkers and can mediate cell–cell communication in renal cell carcinoma. Eur. Urol. Focus 2, 210–218 (2016).
pubmed: 28723537
Crentsil, V. C., Liu, H. & Sellitti, D. F. Comparison of exosomal microRNAs secreted by 786-O clear cell renal carcinoma cells and HK-2 proximal tubule-derived cells in culture identifies microRNA-205 as a potential biomarker of clear cell renal carcinoma. Oncol. Lett. 16, 1285–1290 (2018).
pubmed: 30061948
pmcid: 6063036
De Palma, G. et al. The three-gene signature in urinary extracellular vesicles from patients with clear cell renal cell carcinoma. J. Cancer 7, 1960–1967 (2016).
pubmed: 27877211
pmcid: 5118659
Raimondo, F. et al. Differential protein profiling of renal cell carcinoma urinary exosomes. Mol. Biosyst. 9, 1220–1233 (2013).
pubmed: 23511837
Del Boccio, P. et al. A hyphenated microLC-Q-TOF-MS platform for exosomal lipidomics investigations: application to RCC urinary exosomes. Electrophoresis 33, 689–696 (2012).
pubmed: 22451062
Boyd, L. K., Mao, X. & Lu, Y. J. The complexity of prostate cancer: genomic alterations and heterogeneity. Nat. Rev. Urol. 9, 652–664 (2012).
pubmed: 23132303
Grasso, C. S. et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature 487, 239–243 (2012).
pubmed: 22722839
pmcid: 3396711
Fraser, M. et al. Genomic hallmarks of localized, non-indolent prostate cancer. Nature 541, 359–364 (2017).
pubmed: 28068672
Fitzpatrick, J. M., Banu, E. & Oudard, S. Prostate-specific antigen kinetics in localized and advanced prostate cancer. BJU Int. 103, 578–587 (2009).
pubmed: 19210674
Mottet, N. et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur. Urol. 71, 618–629 (2017).
pubmed: 27568654
pmcid: 27568654
Cornford, P. et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur. Urol. 71, 630–642 (2017).
pubmed: 27591931
Heijnsdijk, E. A. M. et al. Summary statement on screening for prostate cancer in Europe. Int. J. Cancer 142, 741–746 (2018).
pubmed: 29023685
Catalona, W. J. Prostate cancer screening. Med. Clin. North. Am. 102, 199–214 (2018).
pubmed: 29406053
pmcid: 5935113
Antonarakis, E. S. et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl. J. Med. 371, 1028–1038 (2014).
pubmed: 25184630
pmcid: 4201502
Mateo, J. et al. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 373, 1697–1708 (2015).
pubmed: 26510020
pmcid: 5228595
de Bono, J. S. et al. Randomized phase II study evaluating Akt blockade with ipatasertib, in combination with abiraterone, in patients with metastatic prostate cancer with and without PTEN loss. Clin. Cancer Res. 25, 928–936 (2019).
pubmed: 30037818
Luo, J. et al. Role of androgen receptor variants in prostate cancer: report from the 2017 Mission Androgen Receptor Variants Meeting. Eur. Urol. 73, 715–723 (2018).
pubmed: 29258679
Fletcher, C. AR-v7 liquid biopsy for treatment stratification in prostate cancer: how close are we? Curr. Opin. Urol. 27, 500–509 (2017).
pubmed: 28590268
Pan, J., Ding, M., Xu, K., Yang, C. & Mao, L. J. Exosomes in diagnosis and therapy of prostate cancer. Oncotarget 8, 97693–97700 (2017).
pubmed: 29228644
pmcid: 5722596
Valentino, A. et al. Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer. Clin. Transl. Oncol. 19, 651–657 (2017).
pubmed: 28054319
Donovan, M. J. et al. A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result. Prostate Cancer Prostatic Dis. 18, 370–375 (2015).
pubmed: 26345389
Tomlins, S. A. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310, 644–648 (2005).
pubmed: 16254181
Mehra, R. et al. Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Mod. Pathol. 20, 538–544 (2007).
pubmed: 17334343
Berg, K. D. et al. The predictive value of ERG protein expression for development of castration-resistant prostate cancer in hormone-naive advanced prostate cancer treated with primary androgen deprivation therapy. Prostate 75, 1499–1509 (2015).
pubmed: 26053696
de Kok, J. B. et al. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 62, 2695–2698 (2002).
pubmed: 11980670
Hessels, D. et al. DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. Eur. Urol. 44, 8–15; discussion 15–16 (2003).
pubmed: 12814669
Haese, A. et al. Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy. Eur. Urol. 54, 1081–1088 (2008).
pubmed: 18602209
McKiernan, J. et al. A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA Oncol. 2, 882–889 (2016).
pubmed: 27032035
McKiernan, J. et al. A prospective adaptive utility trial to validate performance of a novel urine exosome gene expression assay to predict high-grade prostate cancer in patients with prostate-specific antigen 2-10ng/ml at initial biopsy. Eur. Urol. 74, 731–738 (2018).
pubmed: 30237023
Leyten, G. H. et al. Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur. Urol. 65, 534–542 (2014).
pubmed: 23201468
Tomlins, S. A. et al. Urine TMPRSS2:ERG plus PCA3 for individualized prostate cancer risk assessment. Eur. Urol. 70, 45–53 (2016).
pubmed: 25985884
Antonarakis, E. S. et al. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. OJAMA Oncol. 1, 582–591 (2015).
Del, Re,M. et al. The detection of androgen receptor splice variant 7 in plasma-derived exosomal RNA strongly predicts resistance to hormonal therapy in metastatic prostate cancer patients. Eur. Urol. 71, 680–687 (2017).
Woo, H. K. et al. Urine-based liquid biopsy: non-invasive and sensitive AR-V7 detection in urinary EVs from patients with prostate cancer. Lab. Chip 19, 87–97 (2018).
pubmed: 30500003
Cucchiara, V. et al. Genomic markers in prostate cancer decision making. Eur. Urol. 73, 572–582 (2018).
pubmed: 29129398
Zeuschner, P., Linxweiler, J. & Junker, K. Non-coding RNAs as biomarkers in liquid biopsies with a special emphasis on extracellular vesicles in urological malignancies. Expert. Rev. Mol. Diagn. https://doi.org/10.1080/14737159.2019.1665998 (2019).
Huang, X. et al. Exosomal miR-1290 and miR-375 as prognostic markers in castration-resistant prostate cancer. Eur. Urol. 67, 33–41 (2015).
pubmed: 25129854
Bhagirath, D. et al. MicroRNA-1246 is an exosomal biomarker for aggressive prostate cancer. Cancer Res. 78, 1833–1844 (2018).
pubmed: 29437039
pmcid: 5890910
Endzelins, E. et al. Detection of circulating miRNAs: comparative analysis of extracellular vesicle-incorporated miRNAs and cell-free miRNAs in whole plasma of prostate cancer patients. BMC Cancer 17, 730 (2017).
pubmed: 29121858
pmcid: 5679326
Foj, L. et al. Exosomal and non-exosomal urinary miRNAs in prostate cancer detection and prognosis. Prostate 77, 573–583 (2017).
pubmed: 27990656
Li, Z. et al. Exosomal microRNA-141 is upregulated in the serum of prostate cancer patients. Onco Targets Ther. 9, 139–148 (2016).
pubmed: 26770063
Bryant, R. J. et al. Changes in circulating microRNA levels associated with prostate cancer. Br. J. Cancer 106, 768–774 (2012).
pubmed: 22240788
pmcid: 3322952
Khan, S. et al. Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLOS ONE 7, e46737 (2012).
pubmed: 23091600
pmcid: 3473028
Bijnsdorp, I. V. et al. Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients. J. Extracell. Vesicles 2, 22097 (2013).
Wang, Y. H. et al. Tumor-derived exosomal long noncoding RNAs as promising diagnostic biomarkers for prostate cancer. Cell Physiol. Biochem. 46, 532–545 (2018).
pubmed: 29614511
Clos-Garcia, M. et al. Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression. J. Extracell. Vesicles 7, 1470442 (2018).
pubmed: 29760869
pmcid: 5944373
Skotland, T. et al. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers. Eur. J. Cancer 70, 122–132 (2017).
pubmed: 27914242
Shah, R., Patel, T. & Freedman, J. E. Circulating extracellular vesicles in human disease. N Engl. J. Med. 379, 958–966 (2018).
pubmed: 30184457
Namee, N. M. & O'Driscoll, L. Extracellular vesicles and anti-cancer drug resistance. Biochim. Biophys. Acta Rev. Cancer 1870, 123–136 (2018).
pubmed: 30003999
Webber, J., Yeung, V. & Clayton, A. Extracellular vesicles as modulators of the cancer microenvironment. Semin. Cell Dev. Biol. 40, 27–34 (2015).
pubmed: 25662446
Xu, H. et al. Exosome-transmitted PSMA3 and PSMA3-AS1 promote proteasome inhibitor resistance in multiple myeloma. Clin. Cancer Res. 25, 1923–1935 (2019).
pubmed: 30610101
Binenbaum, Y. et al. Transfer of miRNA in macrophage-derived exosomes induces drug resistance in pancreatic adenocarcinoma. Cancer Res. 78, 5287–5299 (2018).
pubmed: 30042153
Yang, L., Wu, X. H., Wang, D., Luo, C. L. & Chen, L. X. Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell proliferation in vitro. Mol. Med. Rep. 8, 1272–1278 (2013).
pubmed: 23969721
Beckham, C. J. et al. Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression. J. Urol. 192, 583–592 (2014).
pubmed: 24530986
King, H. W., Michael, M. Z. & Gleadle, J. M. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 12, 421 (2012).
pubmed: 22998595
pmcid: 3488584
Kucharzewska, P. et al. Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc. Natl Acad. Sci. USA 110, 7312–7317 (2013).
pubmed: 23589885
pmcid: 3645587
Xue, M., Li, X., Li, Z. & Chen, W. Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1alpha-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol. 35, 6901–6912 (2014).
pubmed: 24737584
Franzen, C. A. et al. Urothelial cells undergo epithelial-to-mesenchymal transition after exposure to muscle invasive bladder cancer exosomes. Oncogenesis 4, e163 (2015).
pubmed: 26280654
pmcid: 4632072
Ostenfeld, M. S. et al. Cellular disposal of miR23b by RAB27-dependent exosome release is linked to acquisition of metastatic properties. Cancer Res. 74, 5758–5771 (2014).
pubmed: 25261234
Goulet, C. R. et al. Exosomes induce fibroblast differentiation into cancer-associated fibroblasts through TGF beta signaling. Mol. Cancer Res. 16, 1196–1204 (2018).
Zhang, L. et al. The 786-0 renal cancer cell-derived exosomes promote angiogenesis by downregulating the expression of hepatocyte cell adhesion molecule. Mol. Med. Rep. 8, 272–276 (2013).
pubmed: 23652371
Jiang, X. L., Zhang, Y., Tan, B., Luo, C. L. & Wu, X. H. Renal tumor-derived exosomes inhibit hepaCAM expression of renal carcinoma cells in a p-AKT-dependent manner. Neoplasma 61, 416–423 (2014).
pubmed: 24645843
Horie, K. et al. Exosomes expressing carbonic anhydrase 9 promote angiogenesis. Biochem. Biophys. Res. Commun. 492, 356–361 (2017).
pubmed: 28851650
Logozzi, M. et al. Prostate cancer cells and exosomes in acidic condition show increased carbonic anhydrase IX expression and activity. J. Enzyme Inhib. Med. Chem. 34, 272–278 (2019).
pubmed: 30734594
pmcid: 6327996
Grange, C. et al. Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche. Cancer Res. 71, 5346–5356 (2011).
pubmed: 21670082
Jingushi, K. et al. Extracellular vesicles isolated from human renal cell carcinoma tissues disrupt vascular endothelial cell morphology via azurocidin. Int. J. Cancer 142, 607–617 (2018).
pubmed: 28975613
Lindoso, R. S., Collino, F. & Camussi, G. Extracellular vesicles derived from renal cancer stem cells induce a pro-tumorigenic phenotype in mesenchymal stromal cells. Oncotarget 6, 7959–7969 (2015).
pubmed: 25797265
pmcid: 4480728
Du, T. et al. Microvesicles derived from human Wharton's jelly mesenchymal stem cells promote human renal cancer cell growth and aggressiveness through induction of hepatocyte growth factor. PLOS ONE 9, e96836 (2014).
pubmed: 24797571
pmcid: 4010513
Xia, Y. et al. Negatively regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway. Oncotarget 8, 37783–37795 (2017).
pubmed: 28384121
pmcid: 5514949
Diao, J. et al. Exosomal Hsp70 mediates immunosuppressive activity of the myeloid-derived suppressor cells via phosphorylation of Stat3. Med. Oncol. 32, 453 (2015).
pubmed: 25603952
Webber, J., Steadman, R., Mason, M. D., Tabi, Z. & Clayton, A. Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res. 70, 9621–9630 (2010).
pubmed: 21098712
Chowdhury, R. et al. Cancer exosomes trigger mesenchymal stem cell differentiation into pro-angiogenic and pro-invasive myofibroblasts. Oncotarget 6, 715–731 (2015).
pubmed: 25596732
Lu, H. et al. Exosomal alphavbeta6 integrin is required for monocyte M2 polarization in prostate cancer. Matrix Biol. 70, 20–35 (2018).
pubmed: 29530483
pmcid: 6081240
Lazaro-Ibanez, E. et al. Metastatic state of parent cells influences the uptake and functionality of prostate cancer cell-derived extracellular vesicles. J. Extracell. Vesicles 6, 1354645 (2017).
pubmed: 28819549
pmcid: 5556667
Singh, A. et al. Exosome-mediated transfer of alphavbeta3 integrin from tumorigenic to nontumorigenic cells promotes a migratory phenotype. Mol. Cancer Res. 14, 1136–1146 (2016).
pubmed: 27439335
pmcid: 5107121
Sanchez, C. A. et al. Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche. Oncotarget 7, 3993–4008 (2016).
pubmed: 26675257
Bilusic, M., Madan, R. A. & Gulley, J. L. Immunotherapy of prostate cancer: facts and hopes. Clin. Cancer Res. 23, 6764–6770 (2017).
pubmed: 28663235
pmcid: 5690854
Gao, J. et al. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat. Med. 23, 551–555 (2017).
pubmed: 28346412
pmcid: 5466900
Lu, X. et al. Effective combinatorial immunotherapy for castration-resistant prostate cancer. Nature 543, 728–732 (2017).
pubmed: 28321130
pmcid: 5374023
Salimu, J. et al. Dominant immunosuppression of dendritic cell function by prostate-cancer-derived exosomes. J. Extracell. Vesicles 6, 1368823 (2017).
pubmed: 28959385
pmcid: 5613918
Clayton, A., Al-Taei, S., Webber, J., Mason, M. D. & Tabi, Z. Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J. Immunol. 187, 676–683 (2011).
pubmed: 21677139
Clayton, A., Mitchell, J. P., Court, J., Mason, M. D. & Tabi, Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res. 67, 7458–7466 (2007).
pubmed: 17671216
Clayton, A. et al. Human tumor-derived exosomes down-modulate NKG2D expression. J. Immunol. 180, 7249–7258 (2008).
pubmed: 18490724
Lundholm, M. et al. Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8
pubmed: 25268476
pmcid: 4182531
Hashimoto, K. et al. Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A. Proc. Natl Acad. Sci. USA 115, 2204–2209 (2018).
pubmed: 29440427
pmcid: 5834702
Ye, Y. et al. Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer. Oncotarget 8, 94834–94849 (2017).
pubmed: 29212270
pmcid: 5706916
Karlsson, T., Lundholm, M., Widmark, A. & Persson, E. Tumor cell-derived exosomes from the prostate cancer cell line TRAMP-C1 impair osteoclast formation and differentiation. PLOS ONE 11, e0166284 (2016).
pubmed: 27832183
pmcid: 5104397
Li, J. et al. Exosome-derived microRNAs contribute to prostate cancer chemoresistance. Int. J. Oncol. 49, 838–846 (2016).
pubmed: 27278879
pmcid: 6904112
Ramteke, A. et al. Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Mol. Carcinog. 54, 554–565 (2015).
pubmed: 24347249
Kumar, D., Gupta, D., Shankar, S. & Srivastava, R. K. Biomolecular characterization of exosomes released from cancer stem cells: possible implications for biomarker and treatment of cancer. Oncotarget 6, 3280–3291 (2015).
pubmed: 25682864
Hosseini-Beheshti, E. et al. Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment. Oncotarget 7, 14639–14658 (2016).
pubmed: 26840259
pmcid: 4924741
Kharmate, G., Hosseini-Beheshti, E., Caradec, J., Chin, M. Y. & Tomlinson Guns, E. S. Epidermal growth factor receptor in prostate cancer derived exosomes. PLOS ONE 11, e0154967 (2016).
pubmed: 27152724
pmcid: 4859494
Corcoran, C. et al. Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLOS ONE 7, e50999 (2012).
pubmed: 23251413
pmcid: 3519481
Kharaziha, P. et al. Molecular profiling of prostate cancer derived exosomes may reveal a predictive signature for response to docetaxel. Oncotarget 6, 21740–21754 (2015).
pubmed: 25844599
pmcid: 4673300
Kawakami, K. et al. Integrin beta4 and vinculin contained in exosomes are potential markers for progression of prostate cancer associated with taxane-resistance. Int. J. Oncol. 47, 384–390 (2015).
pubmed: 25997717
Kato, T. et al. Serum exosomal P-glycoprotein is a potential marker to diagnose docetaxel resistance and select a taxoid for patients with prostate cancer. Urol. Oncol. 33, 385.e15–e20 (2015).
Vagner, T. et al. Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J. Extracell. Vesicles 7, 1505403 (2018).
pubmed: 30108686
pmcid: 6084494
Becker, A. et al. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 30, 836–848 (2016).
pubmed: 27960084
pmcid: 5157696
Schwarzenbach, H., da Silva, A. M., Calin, G. & Pantel, K. Data normalization strategies for microRNA quantification. Clin. Chem. 61, 1333–1342 (2015).
pubmed: 26408530
pmcid: 4890630
Anand, S., Samuel, M., Kumar, S. & Mathivanan, S. Ticket to a bubble ride: cargo sorting into exosomes and extracellular vesicles. Biochim. Biophys. Acta Proteins Proteom. 1867, 140203 (2019).
pubmed: 30822540
Villarroya-Beltri, C., Baixauli, F., Gutierrez-Vazquez, C., Sanchez-Madrid, F. & Mittelbrunn, M. Sorting it out: regulation of exosome loading. Semin. Cancer Biol. 28, 3–13 (2014).
pubmed: 24769058
pmcid: 4640178
Hisey, C. L., Dorayappan, K. D. P., Cohn, D. E., Selvendiran, K. & Hansford, D. J. Microfluidic affinity separation chip for selective capture and release of label-free ovarian cancer exosomes. Lab. Chip 18, 3144–3153 (2018).
pubmed: 30191215
Kanwar, S. S., Dunlay, C. J., Simeone, D. M. & Nagrath, S. Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab. Chip 14, 1891–1900 (2014).
pubmed: 24722878
pmcid: 4134440
Brett, S. I. et al. Immunoaffinity based methods are superior to kits for purification of prostate derived extracellular vesicles from plasma samples. Prostate 77, 1335–1343 (2017).
pubmed: 28762517
Biggs, C. N. et al. Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry. Oncotarget 7, 8839–8849 (2016).
pubmed: 26814433
pmcid: 4891008
Mizutani, K. et al. Isolation of prostate cancer-related exosomes. Anticancer Res. 34, 3419–3423 (2014).
pubmed: 24982349
Welton, J. L. et al. Proteomics analysis of bladder cancer exosomes. Mol. Cell Proteom. 9, 1324–1338 (2010).
Jin, D. et al. ExoAPP: exosome-oriented, aptamer nanoprobe-enabled surface proteins profiling and detection. Anal. Chem. 90, 14402–14411 (2018).
pubmed: 30350954
Castillo, J. et al. Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients. Ann. Oncol. 29, 223–229 (2018).
pubmed: 29045505
Das, C. K. et al. Exosome as a novel shuttle for delivery of therapeutics across biological barriers. Mol. Pharm. 16, 24–40 (2018).
pubmed: 30513203
Hood, J. L. Post isolation modification of exosomes for nanomedicine applications. Nanomedicine 11, 1745–1756 (2016).
pubmed: 27348448
pmcid: 4941124
Ferguson, S. W. & Nguyen, J. Exosomes as therapeutics: the implications of molecular composition and exosomal heterogeneity. J. Control. Release 228, 179–190 (2016).
pubmed: 26941033
Dijkstra, S. et al. Prostate cancer biomarker profiles in urinary sediments and exosomes. J. Urol. 191, 1132–1138 (2014).
pubmed: 24211598
Nilsson, J. et al. Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br. J. Cancer 100, 1603–1607 (2009).
pubmed: 19401683
pmcid: 2696767
Royo, F. et al. Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer. Oncotarget 7, 6835–6846 (2016).
pubmed: 26771841
pmcid: 4872752
Xu, Y. et al. MiR-145 detection in urinary extracellular vesicles increase diagnostic efficiency of prostate cancer based on hydrostatic filtration dialysis method. Prostate 77, 1167–1175 (2017).
pubmed: 28617988
Koppers-Lalic, D. et al. Noninvasive prostate cancer detection by measuring miRNA variants (isomiRs) in urine extracellular vesicles. Oncotarget 7, 22566–22578 (2016).
pubmed: 26992225
pmcid: 5008382
Wani, S., Kaul, D., Mavuduru, R. S., Kakkar, N. & Bhatia, A. Urinary-exosomal miR-2909: a novel pathognomonic trait of prostate cancer severity. J. Biotechnol. 259, 135–139 (2017).
pubmed: 28764970
Rodriguez, M. et al. Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes. Mol. Cancer 16, 156 (2017).
pubmed: 28982366
pmcid: 5629793
Hessvik, N. P., Sandvig, K. & Llorente, A. Exosomal miRNAs as biomarkers for prostate cancer. Front. Genet. 4, 36 (2013).
pubmed: 23519132
pmcid: 3604630
Moltzahn, F. et al. Microfluidic-based multiplex qRT-PCR identifies diagnostic and prognostic microRNA signatures in the sera of prostate cancer patients. Cancer Res. 71, 550–560 (2011).
pubmed: 21098088
Lodes, M. J. et al. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLOS ONE 4, e6229 (2009).
pubmed: 19597549
pmcid: 2704963
Duijvesz, D. et al. Immuno-based detection of extracellular vesicles in urine as diagnostic marker for prostate cancer. Int. J. Cancer 137, 2869–2878 (2015).
pubmed: 26139298
Overbye, A. et al. Identification of prostate cancer biomarkers in urinary exosomes. Oncotarget 6, 30357–30376 (2015).
pubmed: 26196085
pmcid: 4745805
Duijvesz, D. et al. Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer. PLOS ONE 8, e82589 (2013).
pubmed: 24391718
pmcid: 3876995
Li, S. et al. Exosomal ephrinA2 derived from serum as a potential biomarker for prostate cancer. J. Cancer 9, 2659–2665 (2018).
pubmed: 30087706
pmcid: 6072821
Logozzi, M. et al. Increased PSA expression on prostate cancer exosomes in in vitro condition and in cancer patients. Cancer Lett. 403, 318–329 (2017).
pubmed: 28694142
Kawakami, K. et al. Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer. BMC Cancer 17, 316 (2017).
pubmed: 28476099
pmcid: 5420129