Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2017

Open Access 01-12-2017 | Review

A comprehensive overview of exosomes in ovarian cancer: emerging biomarkers and therapeutic strategies

Authors: Lin Cheng, Shuying Wu, Kun Zhang, Yun’an Qing, Tianmin Xu

Published in: Journal of Ovarian Research | Issue 1/2017

Login to get access

Abstract

Exosomes are nanoparticles(40-100 nm) secreted by most cells in the body, which can be isolated from several types of extracellular fluids. It has been shown that exosomes play a key role in intercellular communication and in transportation of genetic information. Emerging evidence shows that exosomes are mediators of metastasis in tumour cells, stromal cells and the extracellular matrix component through the shuttling of cargo, such as proteins, lipids, RNAs, double-stranded DNAs, non-transcribed RNAs, and microRNAs. This phenomenon has been indicated in both tumourigenesis and drug resistance. In this review, we introduce new methods of exosome extraction, focusing on the emerging role of exosomes in ovarian cancer, and discuss their potential clinical applications.
Literature
1.
Trams EG, Lauter CJ, Salem N Jr, Heine U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta. 1981;645:63–70.CrossRefPubMed
2.
Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol. 1983;97:329–39.CrossRefPubMed
3.
Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183:1161–72.CrossRefPubMed
4.
Cho JA, Park H, Lim EH, Kim KH, Choi JS, Lee JH, et al. Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts. Gynecol Oncol. 2011;123:379–86.CrossRefPubMed
5.
Tang MK, Wong AS. Exosomes: emerging biomarkers and targets for ovarian cancer. Cancer Lett. 2015;367:26–33.CrossRefPubMed
6.
Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523:177–82.CrossRefPubMedPubMedCentral
7.
Szajnik M, Czystowska-Kuźmicz M, Elishaev E, Whiteside TL. Biological markers of prognosis, response to therapy and outcome in ovarian carcinoma. Expert Rev Mol Diagn. 2016;16:811–26.CrossRefPubMedPubMedCentral
8.
Keller S, Konig AK, Marme F, Runz S, Wolterink S, Koensgen D, et al. Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. Cancer Lett. 2009;278:73–81.CrossRefPubMed
9.
10.
Lai RC, Yeo RW, Tan KH, Lim SK. Exosomes for drug delivery - a novel application for the mesenchymal stem cell. Biotechnol Adv. 2013;31:543–51.CrossRefPubMed
11.
Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res. 2008;7:5157–66.CrossRefPubMedPubMedCentral
12.
Lasser C, Eldh M, Lotvall J. Isolation and characterization of RNA-containing exosomes. J Vis Exp. 2012;(59):e3037.
13.
Keerthikumar S, Chisanga D, Ariyaratne D, Al Saffar H, Anand S, Zhao K, et al. ExoCarta: a web-based compendium of Exosomal cargo. J Mol Biol. 2016;428:688–92.CrossRefPubMed
14.
Skotland T, Sandvig K, Llorente A. Lipids in exosomes: current knowledge and the way forward. Prog Lipid Res. 2017;66:30–41.CrossRefPubMed
15.
Sato-Kuwabara Y, Melo SA, Soares FA, Calin GA. The fusion of two worlds: non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications (review). Int J Oncol. 2015;46:17–27.CrossRefPubMed
16.
Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 2014;24:766–9.CrossRefPubMedPubMedCentral
17.
Kahlert C, Melo SA, Protopopov A, Tang J, Seth S, Koch M, et al. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem. 2014;289:3869–75.CrossRefPubMedPubMedCentral
18.
Guescini M, Genedani S, Stocchi V, Agnati LF. Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J Neural Transm (Vienna). 2010;117:1–4.CrossRef
19.
Mathivanan S, Fahner CJ, Reid GE, Simpson RJ. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res. 2012;40:D1241–4.CrossRefPubMed
20.
Mathivanan S, Simpson RJ. ExoCarta: a compendium of exosomal proteins and RNA. Proteomics. 2009;9:4997–5000.CrossRefPubMed
21.
Dorayappan KD, Wallbillich JJ, Cohn DE, Selvendiran K. The biological significance and clinical applications of exosomes in ovarian cancer. Gynecol Oncol. 2016;142(1):199–205.
22.
Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, et al. Characterization and proteomic analysis of ovarian cancer-derived exosomes. J Proteome. 2013;80:171–82.CrossRef
23.
Hsu YT, Osmulski P, Wang Y, Huang YW, Liu L, Ruan JH, et al. EpCAM-regulated transcription exerts influences on Nanomechanical properties of endometrial cancer cells that promote epithelial-to-Mesenchymal transition. Cancer Res. 2016;76:6171–82.CrossRefPubMedPubMedCentral
24.
Zhang W, Peng P, Kuang Y, Yang JX, Cao DY, You Y, et al. Characterization of exosomes derived from ovarian cancer cells and normal ovarian epithelial cells by nanoparticle tracking analysis. Tumor Biol. 2016;37:4213–21.CrossRef
25.
Rupp AK, Rupp C, Keller S, Brase JC, Ehehalt R, Fogel M, et al. Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol. 2011;122:437–46.CrossRefPubMed
26.
Li JH, Sherman-Baust CA, Tsai-Turton M, Bristow RE, Roden RB, Morin PJ. Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer. BMC Cancer. 2009;9:244.
27.
Szajnik M, Derbis M, Lach M, Patalas P, Michalak M, Drzewiecka H, et al. Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy. Gynecol Obstet (Sunnyvale, Calif). 2013;Suppl 4:3.
28.
Yin J, Yan X, Yao X, Zhang Y, Shan Y, Mao N, et al. Secretion of annexin A3 from ovarian cancer cells and its association with platinum resistance in ovarian cancer patients. J Cell Mol Med. 2012;16:337–48.CrossRefPubMedPubMedCentral
29.
30.
31.
32.
33.
Mahdian-Shakib A, Dorostkar R, Tat M, Hashemzadeh MS, Saidi N. Differential role of microRNAs in prognosis, diagnosis, and therapy of ovarian cancer. Biomed Pharmacother. 2016;84:592–600.CrossRefPubMed
34.
Meng X, Muller V, Milde-Langosch K, Trillsch F, Pantel K, Schwarzenbach H. Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer. Oncotarget. 2016;7:16923–35.CrossRefPubMedPubMedCentral
35.
Au Yeung CL, Co NN, Tsuruga T, Yeung TL, Kwan SY, Leung CS, et al. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun. 2016;7:11150.CrossRefPubMedPubMedCentral
36.
Ying X, Wu Q, Wu X, Zhu Q, Wang X, Jiang L, et al. Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages. Oncotarget. 2016;7:43076–87.CrossRefPubMedPubMedCentral
37.
Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110:13–21.CrossRefPubMed
38.
Pink RC, Samuel P, Massa D, Caley DP, Brooks SA, Carter DR. The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells. Gynecol Oncol. 2015;137:143–51.CrossRefPubMed
39.
Zhou J, Gong G, Tan H, Dai F, Zhu X, Chen Y, et al. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma. Oncol Rep. 2015;
40.
Enriquez VA, Cleys ER, Da Silveira JC, Spillman MA, Winger QA, Bouma GJ. High LIN28A expressing ovarian cancer cells secrete Exosomes that induce invasion and migration in HEK293 cells. Biomed Res Int. 2015;2015:701390.CrossRefPubMedPubMedCentral
41.
Kobayashi M, Salomon C, Tapia J, Illanes SE, Mitchell MD, Rice GE. Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200. J Transl Med. 2014;12:4.CrossRefPubMedPubMedCentral
42.
Vaksman O, Trope C, Davidson B, Reich R. Exosome-derived miRNAs and ovarian carcinoma progression. Carcinogenesis. 2014;35:2113–20.CrossRefPubMed
43.
Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN, Hughes SM, et al. Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci U S A. 2014;111:14888–93.CrossRefPubMedPubMedCentral
44.
45.
Lea J, Sharma R, Yang F, Zhu H, Ward ES, Schroit AJ. Detection of phosphatidylserine-positive exosomes as a diagnostic marker for ovarian malignancies: a proof of concept study. Oncotarget. 2017;8:14395–407.PubMedPubMedCentral
46.
Escrevente C, Grammel N, Kandzia S, Zeiser J, Tranfield EM, Conradt HS, et al. Sialoglycoproteins and N-glycans from secreted exosomes of ovarian carcinoma cells. PLoS One. 2013;8:e78631.CrossRefPubMedPubMedCentral
47.
Jin Y, Chen K, Wang Z, Wang Y, Liu J, Lin L, et al. DNA in serum extracellular vesicles is stable under different storage conditions. BMC Cancer. 2016;16:753.CrossRefPubMedPubMedCentral
48.
Gold B, Cankovic M, Furtado LV, Meier F, Gocke CD. Do circulating tumor cells, exosomes, and circulating tumor nucleic acids have clinical utility? A report of the association for molecular pathology. J Mol Diagn. 2015;17:209–24.CrossRefPubMedPubMedCentral
49.
Runz S, Keller S, Rupp C, Stoeck A, Issa Y, Koensgen D, et al. Malignant ascites-derived exosomes of ovarian carcinoma patients contain CD24 and EpCAM. Gynecol Oncol. 2007;107:563–71.CrossRefPubMed
50.
Nakamura K, Sawada K, Kinose Y, Yoshimura A, Toda A, Nakatsuka E, et al. Exosomes promote ovarian cancer cell invasion through transfer of CD44 to peritoneal Mesothelial cells. Mol Cancer Res. 2017;15:78–92.CrossRefPubMed
51.
Gutwein P, Stoeck A, Riedle S, Gast D, Runz S, Condon TP, et al. Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells. Clin Cancer Res. 2005;11:2492–501.CrossRefPubMed
52.
Li J, Sherman-Baust CA, Tsai-Turton M, Bristow RE, Roden RB, Morin PJ. Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer. BMC Cancer. 2009;9:244.CrossRefPubMedPubMedCentral
53.
Luo Z, Wang Q, Lau WB, Lau B, Xu L, Zhao L, et al. Tumor microenvironment: the culprit for ovarian cancer metastasis? Cancer Lett. 2016;377:174–82.CrossRefPubMed
54.
Peng P, Yan Y, Keng S. Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity. Oncol Rep. 2011;25:749–62.PubMed
55.
Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One 2010;5:e11469.
56.
Labani-Motlagh A, Israelsson P, Ottander U, Lundin E, Nagaev I, Nagaeva O, et al. Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumour Biol. 2016;37:5455–66.CrossRefPubMed
57.
Robinson-Smith TM, Isaacsohn I, Mercer CA, Zhou M, Van Rooijen N, Husseinzadeh N, et al. Macrophages mediate inflammation-enhanced metastasis of ovarian tumors in mice. Cancer Res. 2007;67:5708–16.CrossRefPubMed
58.
Hu Y, Li D, Wu A, Qiu X, Di W, Huang L, et al. TWEAK-stimulated macrophages inhibit metastasis of epithelial ovarian cancer via exosomal shuttling of microRNA. Cancer Lett. 2017;393:60–7.CrossRefPubMed
59.
Zhang W, Yang J, Cao D, You Y, Shen K, Peng P. Regulation of exosomes released from normal ovarian epithelial cells and ovarian cancer cells. Tumour Biol. 2016;37(12):15763–71.
60.
Hadla M, Palazzolo S, Corona G, Caligiuri I, Canzonieri V, Toffoli G, et al. Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models. Nanomedicine (Lond). 2016;11:2431–41.CrossRef
61.
Reza AM, Choi YJ, Yasuda H, Kim JH. Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells. Sci Rep. 2016;6:38498.CrossRefPubMedPubMedCentral
62.
Shtam TA, Kovalev RA, Varfolomeeva EY, Makarov EM, Kil YV, Filatov MV. Exosomes are natural carriers of exogenous siRNA to human cells in vitro. Cell Commun Signal. 2013;11:88.CrossRefPubMedPubMedCentral
63.
Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:341–5.CrossRefPubMed
64.
65.
Kanlikilicer P, Rashed MH, Bayraktar R, Mitra R, Ivan C, Aslan B, et al. Ubiquitous release of Exosomal tumor suppressor miR-6126 from ovarian cancer cells. Cancer Res. 2016;76:7194–207.CrossRefPubMed
66.
Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P. Delivery of functional anti-miR-9 by Mesenchymal stem cell-derived Exosomes to Glioblastoma Multiforme cells conferred Chemosensitivity. Mol Ther Nucleic Acids. 2013;2:e126.CrossRefPubMedPubMedCentral
67.
Pascucci L, Cocce V, Bonomi A, Ami D, Ceccarelli P, Ciusani E, et al. Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: a new approach for drug delivery. J Control Release. 2014;192:262–70.CrossRefPubMed
68.
Shimbo K, Miyaki S, Ishitobi H, Kato Y, Kubo T, Shimose S, et al. Exosome-formed synthetic microRNA-143 is transferred to osteosarcoma cells and inhibits their migration. Biochem Biophys Res Commun. 2014;445:381–7.CrossRefPubMed
69.
Lee HK, Finniss S, Cazacu S, Bucris E, Ziv-Av A, Xiang C, et al. Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal. Oncotarget. 2013;4:346–61.CrossRefPubMedPubMedCentral
70.
Lou G, Song X, Yang F, Wu S, Wang J, Chen Z, et al. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015;8:122.CrossRefPubMedPubMedCentral
71.
Peterson MF, Otoc N, Sethi JK, Gupta A, Antes TJ. Integrated systems for exosome investigation. Methods. 2015;87:31–45.CrossRefPubMed
72.
Gholizadeh S, Shehata Draz M, Zarghooni M, Sanati-Nezhad A, Ghavami S, Shafiee H, et al. Microfluidic approaches for isolation, detection, and characterization of extracellular vesicles: current status and future directions. Biosens Bioelectron. 2017;91:588–605.CrossRefPubMed
73.
Wang S, Zhang L, Wan S, Cansiz S, Cui C, Liu Y, et al. Aptasensor with expanded nucleotide using DNA Nanotetrahedra for electrochemical detection of cancerous Exosomes. ACS Nano. 2017;11(4):3943–49.
74.
Jeong S, Park J, Pathania D, Castro CM, Weissleder R, Lee H. Integrated magneto-electrochemical sensor for exosome analysis. ACS Nano. 2016;10:1802–9.CrossRefPubMedPubMedCentral
75.
Deregibus MC, Figliolini F, D'Antico S, Manzini PM, Pasquino C, De Lena M, et al. Charge-based precipitation of extracellular vesicles. Int J Mol Med. 2016;38:1359–66.CrossRefPubMedPubMedCentral
76.
Etayash H, McGee AR, Kaur K, Thundat T. Nanomechanical sandwich assay for multiple cancer biomarkers in breast cancer cell-derived exosomes. Nano. 2016;8:15137–41.
77.
Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R, et al. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol. 2014;32:490–5.CrossRefPubMedPubMedCentral
78.
Ziaei P, Geruntho JJ, Marin-Flores OG, Berkman CE, Grant Norton M. Silica nanostructured platform for affinity capture of tumor-derived exosomes. J Mater Sci. 2017;52:6907–16.CrossRef
79.
Xia Y, Liu M, Wang L, Yan A, He W, Chen M, et al. A visible and colorimetric aptasensor based on DNA-capped single-walled carbon nanotubes for detection of exosomes. Biosens Bioelectron. 2017;92:8–15.CrossRefPubMed
80.
Dolatmoradi A, Mirtaheri E, El-Zahab B. Thermo-acoustofluidic separation of vesicles based on cholesterol content. Lab Chip. 2017;17:1332–9.CrossRefPubMed
81.
Wan Y, Cheng G, Liu X, Hao S-J, Nisic M, Zhu C-D, et al. Rapid magnetic isolation of extracellular vesicles via lipid-based nanoprobes. Nature. Biomed Eng. 2017;1:0058.
Metadata
Title
A comprehensive overview of exosomes in ovarian cancer: emerging biomarkers and therapeutic strategies
Authors
Lin Cheng
Shuying Wu
Kun Zhang
Yun’an Qing
Tianmin Xu
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2017
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-017-0368-6

Other articles of this Issue 1/2017

Journal of Ovarian Research 1/2017 Go to the issue

Research

Age is associated with prognosis in serous ovarian carcinoma

Research

Early and consistent overexpression of ADRM1 in ovarian high-grade serous carcinoma

Research

Small leucine-rich proteoglycans (SLRPs) in the endometrium of polycystic ovary syndrome women: a pilot study

Research

Intravenous neutralization of vascular endothelial growth factor reduces vascular function/permeability of the ovary and prevents development of OHSS-like symptoms in rhesus monkeys

Research

Circulatory microRNA 23a and microRNA 23b and polycystic ovary syndrome (PCOS): the effects of body mass index and sex hormones in an Eastern Han Chinese population

Review

Circulating cell-free DNA and circulating tumor cells, the “liquid biopsies” in ovarian cancer