Exosome-based Tumor Therapy: Opportunities and Challenges

Author(s): Chunmei Li, Xiaoming Hou, Peng Zhang, Juan Li, Xiaoguang Liu, Yuping Wang, Quanlin Guan, Yongning Zhou*

Journal Name: Current Drug Metabolism

Volume 21 , Issue 5 , 2020

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Graphical Abstract:


Abstract:

Background: Exosomes play an important role in transferring information among different cell types, as they transport materials from the cell membrane to the cytoplasm. They are involved not only in normal physiological functions, but also in the occurrence and development of a variety of diseases. Cancer is a major health problem affecting humans. Currently, exosomes are considered novel stars in tumor therapy.

Objective: To present a review focusing on the role of exosomes in tumorigenesis and development and the possibility of treating tumors with exosome-targeted therapies or using exosomes as carriers.

Methods: We reviewed literature related to the biological origin and function of exosomes and exosome-tumor relationship.

Results: Exosomes are closely related to tumor immunity, angiogenesis, pre-metastasis microenvironment, chemoresistance, energy metabolism, etc. Tumor therapy involving the targeting of exosomes involves block the generation, secretion, uptake of exosomes, and elimination of circulating exosomes, and develop antitumor vaccines. Exosome as delivery vehicles can be loaded with chemotherapeutic drugs, therapeutic genes, and other therapeutic drugs to target cells. Prospects and challenges of exosome-based tumor therapy are also discussed.

Conclusion: Exosomes are involved in multiple processes during tumor development and should be further studied as novel targets for cancer therapy.

Keywords: Exosomes, delivery vehicles, cancer therapy, chemotherapy, gene therapy, vaccines.

[1]
Johnstone, R.M.; Adam, M.; Hammond, J.R.; Orr, L.; Turbide, C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem., 1987, 262(19), 9412-9420.
[PMID: 3597417]
[2]
Pan, B.T.; Teng, K.; Wu, C.; Adam, M.; Johnstone, R.M. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol., 1985, 101(3), 942-948.
[http://dx.doi.org/10.1083/jcb.101.3.942] [PMID: 2993317]
[3]
Simons, M.; Raposo, G. Exosomes--vesicular carriers for intercellular communication. Curr. Opin. Cell Biol., 2009, 21(4), 575-581.
[http://dx.doi.org/10.1016/j.ceb.2009.03.007] [PMID: 19442504]
[4]
Harding, C.V.; Heuser, J.E.; Stahl, P.D. Exosomes: looking back three decades and into the future. J. Cell Biol., 2013, 200(4), 367-371.
[http://dx.doi.org/10.1083/jcb.201212113] [PMID: 23420870]
[5]
van der Pol, E.; Böing, A.N.; Harrison, P.; Sturk, A.; Nieuwland, R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol. Rev., 2012, 64(3), 676-705.
[http://dx.doi.org/10.1124/pr.112.005983] [PMID: 22722893]
[6]
Raposo, G.; Stoorvogel, W. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol., 2013, 200(4), 373-383.
[http://dx.doi.org/10.1083/jcb.201211138] [PMID: 23420871]
[7]
Théry, C.; Zitvogel, L.; Amigorena, S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol., 2002, 2(8), 569-579.
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
[8]
Conde-Vancells, J.; Rodriguez-Suarez, E.; Embade, N.; Gil, D.; Matthiesen, R.; Valle, M.; Elortza, F.; Lu, S.C.; Mato, J.M.; Falcon-Perez, J.M. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J. Proteome Res., 2008, 7(12), 5157-5166.
[http://dx.doi.org/10.1021/pr8004887] [PMID: 19367702]
[9]
Thery, C.; Amigorena, S.; Raposo, G.; Clayton, A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Prot. Cell. Biol., 2006, Unit 3.22.
[http://dx.doi.org/10.1002/0471143030.cb0322s30]
[10]
Keerthikumar, S.; Chisanga, D.; Ariyaratne, D.; Al Saffar, H.; Anand, S.; Zhao, K.; Samuel, M.; Pathan, M.; Jois, M.; Chilamkurti, N.; Gangoda, L.; Mathivanan, S. ExoCarta: A web-based compendium of exosomal cargo. J. Mol. Biol., 2016, 428(4), 688-692.
[http://dx.doi.org/10.1016/j.jmb.2015.09.019] [PMID: 26434508]
[11]
M, H. R.; Bayraktar, E.; G, K. H.; Abd-Ellah, M. F.; Amero, P.; Chavez-Reyes, A.; Rodriguez-Aguayo, C. Exosomes: from garbage bins to promising therapeutic targets. Int. J. Mol. Sci., 2017, 18(3)
[12]
Hanson, P.I.; Cashikar, A. Multivesicular body morphogenesis. Annu. Rev. Cell Dev. Biol., 2012, 28, 337-362.
[http://dx.doi.org/10.1146/annurev-cellbio-092910-154152] [PMID: 22831642]
[13]
Pegtel, D.M.; Gould, S.J. Exosomes. Annu. Rev. Biochem., 2019, 88, 487-514.
[http://dx.doi.org/10.1146/annurev-biochem-013118-111902] [PMID: 31220978]
[14]
Booth, A.M.; Fang, Y.; Fallon, J.K.; Yang, J.M.; Hildreth, J.E.; Gould, S.J. Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J. Cell Biol., 2006, 172(6), 923-935.
[http://dx.doi.org/10.1083/jcb.200508014] [PMID: 16533950]
[15]
Skotland, T.; Sandvig, K.; Llorente, A. Lipids in exosomes: current knowledge and the way forward. Prog. Lipid Res., 2017, 66, 30-41.
[http://dx.doi.org/10.1016/j.plipres.2017.03.001] [PMID: 28342835]
[16]
Record, M.; Carayon, K.; Poirot, M.; Silvente-Poirot, S. Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim. Biophys. Acta, 2014, 1841(1), 108-120.
[http://dx.doi.org/10.1016/j.bbalip.2013.10.004] [PMID: 24140720]
[17]
Vasconcelos, M.H.; Caires, H.R.; Ābols, A.; Xavier, C.P.R.; Linē, A. Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance. Drug Resist. Updat., 2019, 47, 100647
[http://dx.doi.org/10.1016/j.drup.2019.100647] [PMID: 31704541]
[18]
Ludwig, N.; Whiteside, T.L. Potential roles of tumor-derived exosomes in angiogenesis. Expert Opin. Ther. Targets, 2018, 22(5), 409-417.
[http://dx.doi.org/10.1080/14728222.2018.1464141] [PMID: 29634426]
[19]
Tomasetti, M.; Lee, W.; Santarelli, L.; Neuzil, J. Exosome-derived microRNAs in cancer metabolism: possible implications in cancer diagnostics and therapy. Exp. Mol. Med., 2017, 49(1) e285
[http://dx.doi.org/10.1038/emm.2016.153] [PMID: 28104913]
[20]
Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol., 2007, 9(6), 654-659.
[http://dx.doi.org/10.1038/ncb1596] [PMID: 17486113]
[21]
Marsh, M.; van Meer, G. Cell biology. No ESCRTs for exosomes. Science, 2008, 319(5867), 1191-1192.
[http://dx.doi.org/10.1126/science.1155750] [PMID: 18309064]
[22]
Raiborg, C.; Stenmark, H. The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature, 2009, 458(7237), 445-452.
[http://dx.doi.org/10.1038/nature07961] [PMID: 19325624]
[23]
Theos, A.C.; Truschel, S.T.; Tenza, D.; Hurbain, I.; Harper, D.C.; Berson, J.F.; Thomas, P.C.; Raposo, G.; Marks, M.S. A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. Dev. Cell, 2006, 10(3), 343-354.
[http://dx.doi.org/10.1016/j.devcel.2006.01.012] [PMID: 16516837]
[24]
Buschow, S.I.; Nolte-’t Hoen, E.N.; van Niel, G.; Pols, M.S.; ten Broeke, T.; Lauwen, M.; Ossendorp, F.; Melief, C.J.; Raposo, G.; Wubbolts, R.; Wauben, M.H.; Stoorvogel, W. MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic, 2009, 10(10), 1528-1542.
[http://dx.doi.org/10.1111/j.1600-0854.2009.00963.x] [PMID: 19682328]
[25]
Li, Y.; Zheng, Q.; Bao, C.; Li, S.; Guo, W.; Zhao, J.; Chen, D.; Gu, J.; He, X.; Huang, S. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res., 2015, 25(8), 981-984.
[http://dx.doi.org/10.1038/cr.2015.82] [PMID: 26138677]
[26]
Silva, M.; Melo, S.A. Non-coding RNAs in exosomes: New players in cancer biology. Curr. Genomics, 2015, 16(5), 295-303.
[http://dx.doi.org/10.2174/1389202916666150707154719] [PMID: 27047249]
[27]
Temoche-Diaz, M.M.; Shurtleff, M.J.; Nottingham, R.M.; Yao, J.; Fadadu, R.P.; Lambowitz, A.M.; Schekman, R. Distinct mechanisms of microRNA sorting into cancer cell-derived extracellular vesicle subtypes. eLife, 2019, 8, 8.
[http://dx.doi.org/10.7554/eLife.47544] [PMID: 31436530]
[28]
Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Takeshita, F.; Matsuki, Y.; Ochiya, T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem., 2010, 285(23), 17442-17452.
[http://dx.doi.org/10.1074/jbc.M110.107821] [PMID: 20353945]
[29]
Zhang, J.; Li, S.; Li, L.; Li, M.; Guo, C.; Yao, J.; Mi, S. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics, 2015, 13(1), 17-24.
[http://dx.doi.org/10.1016/j.gpb.2015.02.001] [PMID: 25724326]
[30]
Villarroya-Beltri, C.; Gutiérrez-Vázquez, C.; Sánchez-Cabo, F.; Pérez-Hernández, D.; Vázquez, J.; Martin-Cofreces, N.; Martinez-Herrera, D.J.; Pascual-Montano, A.; Mittelbrunn, M.; Sánchez-Madrid, F. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun., 2013, 4, 2980.
[http://dx.doi.org/10.1038/ncomms3980] [PMID: 24356509]
[31]
Yokoi, A.; Villar-Prados, A.; Oliphint, P.A.; Zhang, J.; Song, X.; De Hoff, P.; Morey, R.; Liu, J.; Roszik, J.; Clise-Dwyer, K.; Burks, J.K.; O’Halloran, T.J.; Laurent, L.C.; Sood, A.K. Mechanisms of nuclear content loading to exosomes. Sci. Adv., 2019, 5(11) eaax8849
[http://dx.doi.org/10.1126/sciadv.aax8849] [PMID: 31799396]
[32]
Federici, C.; Petrucci, F.; Caimi, S.; Cesolini, A.; Logozzi, M.; Borghi, M.; D’Ilio, S.; Lugini, L.; Violante, N.; Azzarito, T.; Majorani, C.; Brambilla, D.; Fais, S. Exosome release and low pH belong to a framework of resistance of human melanoma cells to cisplatin. PLoS One, 2014, 9(2) e88193
[http://dx.doi.org/10.1371/journal.pone.0088193] [PMID: 24516610]
[33]
Savina, A.; Furlán, M.; Vidal, M.; Colombo, M.I. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J. Biol. Chem., 2003, 278(22), 20083-20090.
[http://dx.doi.org/10.1074/jbc.M301642200] [PMID: 12639953]
[34]
Savina, A.; Vidal, M.; Colombo, M.I. The exosome pathway in K562 cells is regulated by Rab11. J. Cell Sci., 2002, 115(Pt 12), 2505-2515.
[PMID: 12045221]
[35]
Ostrowski, M.; Carmo, N.B.; Krumeich, S.; Fanget, I.; Raposo, G.; Savina, A.; Moita, C.F.; Schauer, K.; Hume, A.N.; Freitas, R.P.; Goud, B.; Benaroch, P.; Hacohen, N.; Fukuda, M.; Desnos, C.; Seabra, M.C.; Darchen, F.; Amigorena, S.; Moita, L.F.; Thery, C. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol., 2010, 12(1), 19-30.
[http://dx.doi.org/10.1038/ncb2000]
[36]
Südhof, T.C.; Rothman, J.E. Membrane fusion: grappling with SNARE and SM proteins. Science, 2009, 323(5913), 474-477.
[http://dx.doi.org/10.1126/science.1161748] [PMID: 19164740]
[37]
Fader, C.M.; Sánchez, D.G.; Mestre, M.B.; Colombo, M.I. TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim. Biophys. Acta, 2009, 1793(12), 1901-1916.
[http://dx.doi.org/10.1016/j.bbamcr.2009.09.011] [PMID: 19781582]
[38]
Yang, L.; Peng, X.; Li, Y.; Zhang, X.; Ma, Y.; Wu, C.; Fan, Q.; Wei, S.; Li, H.; Liu, J. Long non-coding RNA HOTAIR promotes exosome secretion by regulating RAB35 and SNAP23 in hepatocellular carcinoma. Mol. Cancer, 2019, 18(1), 78.
[http://dx.doi.org/10.1186/s12943-019-0990-6] [PMID: 30943982]
[39]
Zou, W.; Lai, M.; Zhang, Y.; Zheng, L.; Xing, Z.; Li, T.; Zou, Z.; Song, Q.; Zhao, X.; Xia, L.; Yang, J.; Liu, A.; Zhang, H.; Cui, Z.K.; Jiang, Y.; Bai, X. Exosome release is regulated by mTORC1. Adv. Sci. (Weinh.), 2018, 6(3) 1801313
[http://dx.doi.org/10.1002/advs.201801313] [PMID: 30775228]
[40]
Zomer, A.; Maynard, C.; Verweij, F.J.; Kamermans, A.; Schäfer, R.; Beerling, E.; Schiffelers, R.M.; de Wit, E.; Berenguer, J.; Ellenbroek, S.I.J.; Wurdinger, T.; Pegtel, D.M.; van Rheenen, J. In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell, 2015, 161(5), 1046-1057.
[http://dx.doi.org/10.1016/j.cell.2015.04.042] [PMID: 26000481]
[41]
Kalluri, R. The biology and function of exosomes in cancer. J. Clin. Invest., 2016, 126(4), 1208-1215.
[http://dx.doi.org/10.1172/JCI81135] [PMID: 27035812]
[42]
Mashouri, L.; Yousefi, H.; Aref, A.R.; Ahadi, A.M.; Molaei, F.; Alahari, S.K. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol. Cancer, 2019, 18(1), 75.
[http://dx.doi.org/10.1186/s12943-019-0991-5] [PMID: 30940145]
[43]
Milman, N.; Ginini, L.; Gil, Z. Exosomes and their role in tumorigenesis and anticancer drug resistance. Drug Resist. Updat., 2019, 45, 1-12.
[http://dx.doi.org/10.1016/j.drup.2019.07.003] [PMID: 31369918]
[44]
Sun, W.; Luo, J.D.; Jiang, H.; Duan, D.D. Tumor exosomes: a double-edged sword in cancer therapy. Acta Pharmacol. Sin., 2018, 39(4), 534-541.
[http://dx.doi.org/10.1038/aps.2018.17] [PMID: 29542685]
[45]
Sato, S.; Vasaikar, S.; Eskaros, A.; Kim, Y.; Lewis, J.S.; Zhang, B.; Zijlstra, A.; Weaver, A.M. EPHB2 carried on small extracellular vesicles induces tumor angiogenesis via activation of ephrin reverse signaling. JCI Insight, 2019, 4(23) 132447
[http://dx.doi.org/10.1172/jci.insight.132447] [PMID: 31661464]
[46]
Hsu, Y.L.; Hung, J.Y.; Chang, W.A.; Lin, Y.S.; Pan, Y.C.; Tsai, P.H.; Wu, C.Y.; Kuo, P.L. Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1. Oncogene, 2017, 36(34), 4929-4942.
[http://dx.doi.org/10.1038/onc.2017.105] [PMID: 28436951]
[47]
Bai, M.; Li, J.; Yang, H.; Zhang, H.; Zhou, Z.; Deng, T.; Zhu, K.; Ning, T.; Fan, Q.; Ying, G.; Ba, Y. miR-135b delivered by gastric tumor exosomes inhibits FOXO1 expression in endothelial cells and promotes angiogenesis. Mol. Ther., 2019, 27(10), 1772-1783.
[http://dx.doi.org/10.1016/j.ymthe.2019.06.018] [PMID: 31416776]
[48]
Quail, D.F.; Joyce, J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med., 2013, 19(11), 1423-1437.
[http://dx.doi.org/10.1038/nm.3394] [PMID: 24202395]
[49]
Costa-Silva, B.; Aiello, N.M.; Ocean, A.J.; Singh, S.; Zhang, H.; Thakur, B.K.; Becker, A.; Hoshino, A.; Mark, M.T.; Molina, H.; Xiang, J.; Zhang, T.; Theilen, T.M.; García-Santos, G.; Williams, C.; Ararso, Y.; Huang, Y.; Rodrigues, G.; Shen, T.L.; Labori, K.J.; Lothe, I.M.; Kure, E.H.; Hernandez, J.; Doussot, A.; Ebbesen, S.H.; Grandgenett, P.M.; Hollingsworth, M.A.; Jain, M.; Mallya, K.; Batra, S.K.; Jarnagin, W.R.; Schwartz, R.E.; Matei, I.; Peinado, H.; Stanger, B.Z.; Bromberg, J.; Lyden, D. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol., 2015, 17(6), 816-826.
[http://dx.doi.org/10.1038/ncb3169] [PMID: 25985394]
[50]
Dai, J.; Escara-Wilke, J.; Keller, J.M.; Jung, Y.; Taichman, R.S.; Pienta, K.J.; Keller, E.T. Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis. J. Exp. Med., 2019, 216(12), 2883-2899.
[http://dx.doi.org/10.1084/jem.20190158] [PMID: 31548301]
[51]
Rodrigues, G.; Hoshino, A.; Kenific, C.M.; Matei, I.R.; Steiner, L.; Freitas, D.; Kim, H.S.; Oxley, P.R.; Scandariato, I.; Casanova-Salas, I.; Dai, J.; Badwe, C.R.; Gril, B.; Tešić Mark, M.; Dill, B.D.; Molina, H.; Zhang, H.; Benito-Martin, A.; Bojmar, L.; Ararso, Y.; Offer, K.; LaPlant, Q.; Buehring, W.; Wang, H.; Jiang, X.; Lu, T.M.; Liu, Y.; Sabari, J.K.; Shin, S.J.; Narula, N.; Ginter, P.S.; Rajasekhar, V.K.; Healey, J.H.; Meylan, E.; Costa-Silva, B.; Wang, S.E.; Rafii, S.; Altorki, N.K.; Rudin, C.M.; Jones, D.R.; Steeg, P.S.; Peinado, H.; Ghajar, C.M.; Bromberg, J.; de Sousa, M.; Pisapia, D.; Lyden, D. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. Nat. Cell Biol., 2019, 21(11), 1403-1412.
[http://dx.doi.org/10.1038/s41556-019-0404-4] [PMID: 31685984]
[52]
Zhang, L.; Zhang, S.; Yao, J.; Lowery, F.J.; Zhang, Q.; Huang, W.C.; Li, P.; Li, M.; Wang, X.; Zhang, C.; Wang, H.; Ellis, K.; Cheerathodi, M.; McCarty, J.H.; Palmieri, D.; Saunus, J.; Lakhani, S.; Huang, S.; Sahin, A.A.; Aldape, K.D.; Steeg, P.S.; Yu, D. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature, 2015, 527(7576), 100-104.
[http://dx.doi.org/10.1038/nature15376] [PMID: 26479035]
[53]
Au Yeung, C.L.; Co, N.N.; Tsuruga, T.; Yeung, T.L.; Kwan, S.Y.; Leung, C.S.; Li, Y.; Lu, E.S.; Kwan, K.; Wong, K.K.; Schmandt, R.; Lu, K.H.; Mok, S.C. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat. Commun., 2016, 7, 11150.
[http://dx.doi.org/10.1038/ncomms11150] [PMID: 27021436]
[54]
Mikamori, M.; Yamada, D.; Eguchi, H.; Hasegawa, S.; Kishimoto, T.; Tomimaru, Y.; Asaoka, T.; Noda, T.; Wada, H.; Kawamoto, K.; Gotoh, K.; Takeda, Y.; Tanemura, M.; Mori, M.; Doki, Y. MicroRNA-155 controls exosome synthesis and promotes gemcitabine resistance in pancreatic ductal adenocarcinoma. Sci. Rep., 2017, 7(1), 42339.
[http://dx.doi.org/10.1038/srep42339] [PMID: 28198398]
[55]
Richards, K.E.; Zeleniak, A.E.; Fishel, M.L.; Wu, J.; Littlepage, L.E.; Hill, R. Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene, 2017, 36(13), 1770-1778.
[http://dx.doi.org/10.1038/onc.2016.353] [PMID: 27669441]
[56]
Qin, X.; Yu, S.; Zhou, L.; Shi, M.; Hu, Y.; Xu, X.; Shen, B.; Liu, S.; Yan, D.; Feng, J. Cisplatin-resistant lung cancer cell-derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100-5p-dependent manner. Int. J. Nanomedicine, 2017, 12, 3721-3733.
[http://dx.doi.org/10.2147/IJN.S131516] [PMID: 28553110]
[57]
Safaei, R.; Larson, B.J.; Cheng, T.C.; Gibson, M.A.; Otani, S.; Naerdemann, W.; Howell, S.B. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol. Cancer Ther., 2005, 4(10), 1595-1604.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0102] [PMID: 16227410]
[58]
Khoo, X.H.; Paterson, I.C.; Goh, B.H.; Lee, W.L. Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles. Cancers (Basel), 2019, 11(8) E1166
[http://dx.doi.org/10.3390/cancers11081166] [PMID: 31416147]
[59]
Marleau, A.M.; Chen, C.S.; Joyce, J.A.; Tullis, R.H. Exosome removal as a therapeutic adjuvant in cancer. J. Transl. Med., 2012, 10, 134.
[http://dx.doi.org/10.1186/1479-5876-10-134] [PMID: 22738135]
[60]
Raposo, G.; Nijman, H.W.; Stoorvogel, W.; Liejendekker, R.; Harding, C.V.; Melief, C.J.; Geuze, H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med., 1996, 183(3), 1161-1172.
[http://dx.doi.org/10.1084/jem.183.3.1161] [PMID: 8642258]
[61]
Czernek, L.; Düchler, M. Functions of cancer-derived extracellular vesicles in immunosuppression. Arch. Immunol. Ther. Exp. (Warsz.), 2017, 65(4), 311-323.
[http://dx.doi.org/10.1007/s00005-016-0453-3] [PMID: 28101591]
[62]
Zhang, H.G.; Grizzle, W.E. Exosomes and cancer: a newly described pathway of immune suppression. Clin. Cancer Res., 2011, 17(5), 959-964.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-1489] [PMID: 21224375]
[63]
Rafi, M.A.; Omidi, Y. A prospective highlight on exosomal nanoshuttles and cancer immunotherapy and vaccination. Bioimpacts, 2015, 5(3), 117-122.
[http://dx.doi.org/10.15171/bi.2015.22] [PMID: 26457248]
[64]
Czystowska-Kuzmicz, M.; Sosnowska, A.; Nowis, D.; Ramji, K.; Szajnik, M.; Chlebowska-Tuz, J.; Wolinska, E.; Gaj, P.; Grazul, M.; Pilch, Z.; Zerrouqi, A.; Graczyk-Jarzynka, A.; Soroczynska, K.; Cierniak, S.; Koktysz, R.; Elishaev, E.; Gruca, S.; Stefanowicz, A.; Blaszczyk, R.; Borek, B.; Gzik, A.; Whiteside, T.; Golab, J. Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma. Nat. Commun., 2019, 10(1), 3000.
[http://dx.doi.org/10.1038/s41467-019-10979-3] [PMID: 31278254]
[65]
Fabbri, M. Natural killer cell-derived vesicular miRNAs: A new anticancer approach? Cancer Res., 2020, 80(1), 17-22.
[PMID: 31672842]
[66]
Cianciaruso, C.; Beltraminelli, T.; Duval, F.; Nassiri, S.; Hamelin, R.; Mozes, A.; Gallart-Ayala, H.; Ceada Torres, G.; Torchia, B.; Ries, C. H.; Ivanisevic, J.; De Palma, M. Molecular profiling and functional analysis of macrophage-derived tumor extracellular vesicles. Cell Rep., 2019, 27(10), 3062-3080. e11
[http://dx.doi.org/10.1016/j.celrep.2019.05.008]
[67]
Zhao, H.; Yang, L.; Baddour, J.; Achreja, A.; Bernard, V.; Moss, T.; Marini, J.C.; Tudawe, T.; Seviour, E.G.; San Lucas, F.A.; Alvarez, H.; Gupta, S.; Maiti, S.N.; Cooper, L.; Peehl, D.; Ram, P.T.; Maitra, A.; Nagrath, D. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. eLife, 2016, 5, e10250
[http://dx.doi.org/10.7554/eLife.10250] [PMID: 26920219]
[68]
Fong, M.Y.; Zhou, W.; Liu, L.; Alontaga, A.Y.; Chandra, M.; Ashby, J.; Chow, A.; O’Connor, S.T.; Li, S.; Chin, A.R.; Somlo, G.; Palomares, M.; Li, Z.; Tremblay, J.R.; Tsuyada, A.; Sun, G.; Reid, M.A.; Wu, X.; Swiderski, P.; Ren, X.; Shi, Y.; Kong, M.; Zhong, W.; Chen, Y.; Wang, S.E. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat. Cell Biol., 2015, 17(2), 183-194.
[http://dx.doi.org/10.1038/ncb3094] [PMID: 25621950]
[69]
Sung, J.S.; Kang, C.W.; Kang, S.; Jang, Y.; Chae, Y.C.; Kim, B.G.; Cho, N.H. ITGB4-mediated metabolic reprogramming of cancer-associated fibroblasts. Oncogene, 2020, 39, 664-676.
[PMID: 31534187]
[70]
Vermeer, P.D. Exosomal induction of tumor innervation. Cancer Res., 2019, 79(14), 3529-3535.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-3995] [PMID: 31088834]
[71]
Stefanius, K.; Servage, K.; de Souza Santos, M.; Gray, H.F.; Toombs, J.E.; Chimalapati, S.; Kim, M.S.; Malladi, V.S.; Brekken, R.; Orth, K. Human pancreatic cancer cell exosomes, but not human normal cell exosomes, act as an initiator in cell transformation. eLife, 2019, 8, 8.
[http://dx.doi.org/10.7554/eLife.40226] [PMID: 31134894]
[72]
Hwang, W.L.; Lan, H.Y.; Cheng, W.C.; Huang, S.C.; Yang, M.H. Tumor stem-like cell-derived exosomal RNAs prime neutrophils for facilitating tumorigenesis of colon cancer. J. Hematol. Oncol., 2019, 12(1), 10.
[http://dx.doi.org/10.1186/s13045-019-0699-4] [PMID: 30683126]
[73]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[74]
Datta, A.; Kim, H.; Lal, M.; McGee, L.; Johnson, A.; Moustafa, A.A.; Jones, J.C.; Mondal, D.; Ferrer, M.; Abdel-Mageed, A.B. Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells. Cancer Lett., 2017, 408, 73-81.
[http://dx.doi.org/10.1016/j.canlet.2017.08.020] [PMID: 28844715]
[75]
Datta, A.; Kim, H.; McGee, L.; Johnson, A.E.; Talwar, S.; Marugan, J.; Southall, N.; Hu, X.; Lal, M.; Mondal, D.; Ferrer, M.; Abdel-Mageed, A.B. High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer. Sci. Rep., 2018, 8(1), 8161.
[http://dx.doi.org/10.1038/s41598-018-26411-7] [PMID: 29802284]
[76]
Im, E.J.; Lee, C.H.; Moon, P.G.; Rangaswamy, G.G.; Lee, B.; Lee, J.M.; Lee, J.C.; Jee, J.G.; Bae, J.S.; Kwon, T.K.; Kang, K.W.; Jeong, M.S.; Lee, J.E.; Jung, H.S.; Ro, H.J.; Jun, S.; Kang, W.; Seo, S.Y.; Cho, Y.E.; Song, B.J.; Baek, M.C. Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A. Nat. Commun., 2019, 10(1), 1387.
[http://dx.doi.org/10.1038/s41467-019-09387-4] [PMID: 30918259]
[77]
Zuo, L.; Xie, Y.; Tang, J.; Xin, S.; Liu, L.; Zhang, S.; Yan, Q.; Zhu, F.; Lu, J. Targeting exosomal EBV-LMP1 transfer and miR-203 expression via the NF-κB pathway: the therapeutic role of aspirin in NPC. Mol. Ther. Nucleic Acids, 2019, 17, 175-184.
[http://dx.doi.org/10.1016/j.omtn.2019.05.023] [PMID: 31265948]
[78]
Chalmin, F.; Ladoire, S.; Mignot, G.; Vincent, J.; Bruchard, M.; Remy-Martin, J-P.; Boireau, W.; Rouleau, A.; Simon, B.; Lanneau, D.; De Thonel, A.; Multhoff, G.; Hamman, A.; Martin, F.; Chauffert, B.; Solary, E.; Zitvogel, L.; Garrido, C.; Ryffel, B.; Borg, C.; Apetoh, L.; Rébé, C.; Ghiringhelli, F. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J. Clin. Invest., 2010, 120(2), 457-471.
[http://dx.doi.org/10.1172/JCI40483] [PMID: 20093776]
[79]
Christianson, H.C.; Svensson, K.J.; van Kuppevelt, T.H.; Li, J.P.; Belting, M. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc. Natl. Acad. Sci. USA, 2013, 110(43), 17380-17385.
[http://dx.doi.org/10.1073/pnas.1304266110] [PMID: 24101524]
[80]
Nishida-Aoki, N.; Tominaga, N.; Takeshita, F.; Sonoda, H.; Yoshioka, Y.; Ochiya, T. Disruption of circulating extracellular vesicles as a novel therapeutic strategy against cancer metastasis. Mol. Ther., 2017, 25(1), 181-191.
[http://dx.doi.org/10.1016/j.ymthe.2016.10.009] [PMID: 28129113]
[81]
Xie, X.; Nie, H.; Zhou, Y.; Lian, S.; Mei, H.; Lu, Y.; Dong, H.; Li, F.; Li, T.; Li, B.; Wang, J.; Lin, M.; Wang, C.; Shao, J.; Gao, Y.; Chen, J.; Xie, F.; Jia, L. Eliminating blood oncogenic exosomes into the small intestine with aptamer-functionalized nanoparticles. Nat. Commun., 2019, 10(1), 5476.
[http://dx.doi.org/10.1038/s41467-019-13316-w] [PMID: 31792209]
[82]
Yang, L.; Han, D.; Zhan, Q.; Li, X.; Shan, P.; Hu, Y.; Ding, H.; Wang, Y.; Zhang, L.; Zhang, Y.; Xue, S.; Zhao, J.; Hou, X.; Wang, Y.; Li, P.; Yuan, X.; Qi, H. Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy. Theranostics, 2019, 9(25), 7680-7696.
[http://dx.doi.org/10.7150/thno.37220] [PMID: 31695794]
[83]
Sprooten, J.; Ceusters, J.; Coosemans, A.; Agostinis, P.; De Vleeschouwer, S.; Zitvogel, L.; Kroemer, G.; Galluzzi, L.; Garg, A.D. Trial watch: dendritic cell vaccination for cancer immunotherapy. OncoImmunology, 2019, 8(11) e1638212
[http://dx.doi.org/10.1080/2162402X.2019.1638212] [PMID: 31646087]
[84]
Morse, M.A.; Garst, J.; Osada, T.; Khan, S.; Hobeika, A.; Clay, T.M.; Valente, N.; Shreeniwas, R.; Sutton, M.A.; Delcayre, A.; Hsu, D.H.; Le Pecq, J.B.; Lyerly, H.K. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J. Transl. Med., 2005, 3(1), 9.
[http://dx.doi.org/10.1186/1479-5876-3-9] [PMID: 15723705]
[85]
Besse, B.; Charrier, M.; Lapierre, V.; Dansin, E.; Lantz, O.; Planchard, D.; Le Chevalier, T.; Livartoski, A.; Barlesi, F.; Laplanche, A.; Ploix, S.; Vimond, N.; Peguillet, I.; Théry, C.; Lacroix, L.; Zoernig, I.; Dhodapkar, K.; Dhodapkar, M.; Viaud, S.; Soria, J.C.; Reiners, K.S.; Pogge von Strandmann, E.; Vély, F.; Rusakiewicz, S.; Eggermont, A.; Pitt, J.M.; Zitvogel, L.; Chaput, N. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. OncoImmunology, 2015, 5(4) e1071008
[http://dx.doi.org/10.1080/2162402X.2015.1071008] [PMID: 27141373]
[86]
Pineda, B.; Sánchez García, F.J.; Olascoaga, N.K.; Pérez de la Cruz, V.; Salazar, A.; Moreno-Jiménez, S.; Hernández Pedro, N.; Márquez-Navarro, A.; Ortiz Plata, A.; Sotelo, J. Malignant glioma therapy by vaccination with irradiated C6 cell-derived microvesicles promotes an antitumoral immune response. Mol. Ther., 2019, 27(9), 1612-1620.
[http://dx.doi.org/10.1016/j.ymthe.2019.05.016] [PMID: 31204210]
[87]
Morishita, M.; Takahashi, Y.; Matsumoto, A.; Nishikawa, M.; Takakura, Y. Exosome-based tumor antigens-adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA. Biomaterials, 2016, 111, 55-65.
[http://dx.doi.org/10.1016/j.biomaterials.2016.09.031] [PMID: 27723556]
[88]
Cheng, L.; Wang, Y.; Huang, L. Exosomes from M1-polarized macrophages potentiate the cancer vaccine by creating a pro-inflammatory microenvironment in the lymph node. Mol. Ther., 2017, 25(7), 1665-1675.
[http://dx.doi.org/10.1016/j.ymthe.2017.02.007] [PMID: 28284981]
[89]
Zitvogel, L.; Regnault, A.; Lozier, A.; Wolfers, J.; Flament, C.; Tenza, D.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med., 1998, 4(5), 594-600.
[http://dx.doi.org/10.1038/nm0598-594] [PMID: 9585234]
[90]
Rosenblum, D.; Joshi, N.; Tao, W.; Karp, J.M.; Peer, D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat. Commun., 2018, 9(1), 1410.
[http://dx.doi.org/10.1038/s41467-018-03705-y] [PMID: 29650952]
[91]
Chauhan, S.; Danielson, S.; Clements, V.; Edwards, N.; Ostrand-Rosenberg, S.; Fenselau, C. Surface glycoproteins of exosomes Shed by Myeloid-Derived Suppressor Cells Contribute to Function. J. Proteome Res., 2017, 16(1), 238-246.
[http://dx.doi.org/10.1021/acs.jproteome.6b00811] [PMID: 27728760]
[92]
Haraszti, R.A.; Didiot, M.C.; Sapp, E.; Leszyk, J.; Shaffer, S.A.; Rockwell, H.E.; Gao, F.; Narain, N.R.; DiFiglia, M.; Kiebish, M.A.; Aronin, N.; Khvorova, A. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J. Extracell. Vesicles, 2016, 5, 32570.
[http://dx.doi.org/10.3402/jev.v5.32570] [PMID: 27863537]
[93]
Sato, Y.T.; Umezaki, K.; Sawada, S.; Mukai, S.A.; Sasaki, Y.; Harada, N.; Shiku, H.; Akiyoshi, K. Engineering hybrid exosomes by membrane fusion with liposomes. Sci. Rep., 2016, 6, 21933.
[http://dx.doi.org/10.1038/srep21933] [PMID: 26911358]
[94]
Zhu, Q.; Ling, X.; Yang, Y.; Zhang, J.; Li, Q.; Niu, X.; Hu, G.; Chen, B.; Li, H.; Wang, Y.; Deng, Z. Embryonic stem cells-derived exosomes endowed with targeting properties as chemotherapeutics delivery vehicles for glioblastoma therapy. Adv. Sci. (Weinh.), 2019, 6(6) 1801899
[http://dx.doi.org/10.1002/advs.201801899] [PMID: 30937268]
[95]
Pi, F.; Binzel, D.W.; Lee, T.J.; Li, Z.; Sun, M.; Rychahou, P.; Li, H.; Haque, F.; Wang, S.; Croce, C.M.; Guo, B.; Evers, B.M.; Guo, P. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nat. Nanotechnol., 2018, 13(1), 82-89.
[http://dx.doi.org/10.1038/s41565-017-0012-z] [PMID: 29230043]
[96]
Zhang, P.; Dong, B.; Zeng, E.; Wang, F.; Jiang, Y.; Li, D.; Liu, D. In vivo tracking of multiple tumor exosomes labeled by phospholipid-based bioorthogonal conjugation. Anal. Chem., 2018, 90(19), 11273-11279.
[http://dx.doi.org/10.1021/acs.analchem.8b01506] [PMID: 30178994]
[97]
Hoshino, A.; Costa-Silva, B.; Shen, T.L.; Rodrigues, G.; Hashimoto, A.; Tesic Mark, M.; Molina, H.; Kohsaka, S.; Di Giannatale, A.; Ceder, S.; Singh, S.; Williams, C.; Soplop, N.; Uryu, K.; Pharmer, L.; King, T.; Bojmar, L.; Davies, A.E.; Ararso, Y.; Zhang, T.; Zhang, H.; Hernandez, J.; Weiss, J.M.; Dumont-Cole, V.D.; Kramer, K.; Wexler, L.H.; Narendran, A.; Schwartz, G.K.; Healey, J.H.; Sandstrom, P.; Labori, K.J.; Kure, E.H.; Grandgenett, P.M.; Hollingsworth, M.A.; de Sousa, M.; Kaur, S.; Jain, M.; Mallya, K.; Batra, S.K.; Jarnagin, W.R.; Brady, M.S.; Fodstad, O.; Muller, V.; Pantel, K.; Minn, A.J.; Bissell, M.J.; Garcia, B.A.; Kang, Y.; Rajasekhar, V.K.; Ghajar, C.M.; Matei, I.; Peinado, H.; Bromberg, J.; Lyden, D. Tumour exosome integrins determine organotropic metastasis. Nature, 2015, 527(7578), 329-335.
[http://dx.doi.org/10.1038/nature15756] [PMID: 26524530]
[98]
Kooijmans, S.A.; Aleza, C.G.; Roffler, S.R.; van Solinge, W.W.; Vader, P.; Schiffelers, R.M. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting. J. Extracell. Vesicles, 2016, 5, 31053.
[http://dx.doi.org/10.3402/jev.v5.31053] [PMID: 26979463]
[99]
Morad, G.; Carman, C.V.; Hagedorn, E.J.; Perlin, J.R.; Zon, L.I.; Mustafaoglu, N.; Park, T.E.; Ingber, D.E.; Daisy, C.C.; Moses, M.A. Tumor-derived extracellular vesicles breach the intact blood-brain barrier via transcytosis. ACS Nano, 2019, 13(12), 13853-13865.
[http://dx.doi.org/10.1021/acsnano.9b04397] [PMID: 31479239]
[100]
Kim, G.; Kim, M.; Lee, Y.; Byun, J.W.; Hwang, D.W.; Lee, M. Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes. J. Control. Release, 2020, 317, 273-281.
[http://dx.doi.org/10.1016/j.jconrel.2019.11.009] [PMID: 31730913]
[101]
Kim, M.S.; Haney, M.J.; Zhao, Y.; Mahajan, V.; Deygen, I.; Klyachko, N.L.; Inskoe, E.; Piroyan, A.; Sokolsky, M.; Okolie, O.; Hingtgen, S.D.; Kabanov, A.V.; Batrakova, E.V. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine (Lond.), 2016, 12(3), 655-664.
[http://dx.doi.org/10.1016/j.nano.2015.10.012] [PMID: 26586551]
[102]
Kim, M.S.; Haney, M.J.; Zhao, Y.; Yuan, D.; Deygen, I.; Klyachko, N.L.; Kabanov, A.V.; Batrakova, E.V. Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations. Nanomedicine (Lond.), 2018, 14(1), 195-204.
[http://dx.doi.org/10.1016/j.nano.2017.09.011] [PMID: 28982587]
[103]
Agrawal, A.K.; Aqil, F.; Jeyabalan, J.; Spencer, W.A.; Beck, J.; Gachuki, B.W.; Alhakeem, S.S.; Oben, K.; Munagala, R.; Bondada, S.; Gupta, R.C. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine (Lond.), 2017, 13(5), 1627-1636.
[http://dx.doi.org/10.1016/j.nano.2017.03.001] [PMID: 28300659]
[104]
Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J.A. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol., 2011, 29(4), 341-345.
[http://dx.doi.org/10.1038/nbt.1807] [PMID: 21423189]
[105]
Kamerkar, S.; LeBleu, V.S.; Sugimoto, H.; Yang, S.; Ruivo, C.F.; Melo, S.A.; Lee, J.J.; Kalluri, R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature, 2017, 546(7659), 498-503.
[http://dx.doi.org/10.1038/nature22341] [PMID: 28607485]
[106]
Bellavia, D.; Raimondo, S.; Calabrese, G.; Forte, S.; Cristaldi, M.; Patinella, A.; Memeo, L.; Manno, M.; Raccosta, S.; Diana, P.; Cirrincione, G.; Giavaresi, G.; Monteleone, F.; Fontana, S.; De Leo, G.; Alessandro, R. Interleukin 3- receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous Leukemia cell growth. Theranostics, 2017, 7(5), 1333-1345.
[http://dx.doi.org/10.7150/thno.17092] [PMID: 28435469]
[107]
Kim, S.M.; Yang, Y.; Oh, S.J.; Hong, Y.; Seo, M.; Jang, M. Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting. J. Control. Release, 2017, 266, 8-16.
[http://dx.doi.org/10.1016/j.jconrel.2017.09.013] [PMID: 28916446]
[108]
Fu, W.; Lei, C.; Liu, S.; Cui, Y.; Wang, C.; Qian, K.; Li, T.; Shen, Y.; Fan, X.; Lin, F.; Ding, M.; Pan, M.; Ye, X.; Yang, Y.; Hu, S. CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity. Nat. Commun., 2019, 10(1), 4355.
[http://dx.doi.org/10.1038/s41467-019-12321-3] [PMID: 31554797]
[109]
Wang, G.; Hu, W.; Chen, H.; Shou, X.; Ye, T.; Xu, Y. Cocktail strategy based on NK cell-derived exosomes and their biomimetic nanoparticles for dual tumor therapy. Cancers (Basel), 2019, 11(10) E1560
[http://dx.doi.org/10.3390/cancers11101560] [PMID: 31615145]
[110]
Mendt, M.; Kamerkar, S.; Sugimoto, H.; McAndrews, K.M.; Wu, C.C.; Gagea, M.; Yang, S.; Blanko, E.V.R.; Peng, Q.; Ma, X.; Marszalek, J.R.; Maitra, A.; Yee, C.; Rezvani, K.; Shpall, E.; LeBleu, V.S.; Kalluri, R. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight, 2018, 3(8), 99263.
[http://dx.doi.org/10.1172/jci.insight.99263] [PMID: 29669940]


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