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

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2018

Open Access 01-12-2018 | Review

Extracellular vesicles as mediators of the progression and chemoresistance of pancreatic cancer and their potential clinical applications

Authors: Jiangdong Qiu, Gang Yang, Mengyu Feng, Suli Zheng, Zhe Cao, Lei You, Lianfang Zheng, Taiping Zhang, Yupei Zhao

Published in: Molecular Cancer | Issue 1/2018

Login to get access

Abstract

Pancreatic cancer is one of the most lethal cancers worldwide due to its insidious symptoms, early metastasis, and chemoresistance. Hence, the underlying mechanisms contributing to pancreatic cancer progression require further exploration. Based on accumulating evidence, extracellular vesicles, including exosomes and microvesicles, play a crucial role in pancreatic cancer progression and chemoresistance. Furthermore, they also possess the potential to be promising biomarkers, therapy targets and tools for treating pancreatic cancer. Therefore, in-depth studies on the role of extracellular vesicles in pancreatic cancer are meaningful. In this review, we focus on the regulatory effects of extracellular vesicles on pancreatic cancer progression, metastasis, cancer-related immunity and chemoresistance, particularly their potential roles as biomarkers and therapeutic targets.
Literature
1.
2.
Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, XQ Y, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.PubMedCrossRef
3.
Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17:816–26.PubMedCrossRef
4.
5.
Nuzhat Z, Kinhal V, Sharma S, Rice GE, Joshi V, Salomon C. Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression. Oncotarget. 2017;8:17279–91.PubMed
6.
7.
Matsushita H, Yang YM, Pandol SJ, Seki E. Exosome migration inhibitory factor as a marker and therapeutic target for pancreatic cancer. Gastroenterology. 2016;150:1033–5.PubMedPubMedCentralCrossRef
8.
Xiong G, Feng M, Yang G, Zheng S, Song X, Cao Z, You L, Zheng L, Hu Y, Zhang T, Zhao Y. The underlying mechanisms of non-coding RNAs in the chemoresistance of pancreatic cancer. Cancer Lett. 2017;397:94–102.PubMedCrossRef
9.
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, et al. MicroRNA-155 controls exosome synthesis and promotes gemcitabine resistance in pancreatic ductal adenocarcinoma. Sci Rep. 2017;7:42339.PubMedPubMedCentralCrossRef
10.
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.PubMedCrossRef
11.
12.
Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987;262:9412–20.PubMed
13.
Lotvall J, Hill AF, Hochberg F, Buzas EI, Di Vizio D, Gardiner C, Gho YS, Kurochkin IV, Mathivanan S, Quesenberry P, Sahoo S, Tahara H, Wauben MH, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 2014;3:26913.PubMedCrossRef
14.
Silva AM, Almeida MI, Teixeira JH, Maia AF, Calin GA, Barbosa MA, Santos SG. Dendritic cell-derived extracellular vesicles mediate mesenchymal stem/stromal cell recruitment. Sci Rep. 2017;7:1667.PubMedPubMedCentralCrossRef
15.
Mazzeo C, Calvo V, Alonso R, Merida I, Izquierdo M. Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes. Cell Death Differ. 2016;23:99–109.PubMedCrossRef
16.
Von Bartheld CS, Altick AL. Multivesicular bodies in neurons: distribution, protein content, and trafficking functions. Prog Neurobiol. 2011;93:313–40.PubMedPubMedCentralCrossRef
17.
Donnarumma E, Fiore D, Nappa M, Roscigno G, Adamo A, Iaboni M, Russo V, Affinito A, Puoti I, Quintavalle C, Rienzo A, Piscuoglio S, Thomas R, et al. Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer. Oncotarget. 2017;8:19592–608.PubMedPubMedCentral
18.
Burrello J, Monticone S, Gai C, Gomez Y, Kholia S, Camussi G. Stem cell-derived extracellular vesicles and immune-modulation. Front Cell Dev Biol. 2016;4:83.PubMedPubMedCentralCrossRef
19.
Li Y, Yang Y, Xiong A, Wu X, Xie J, Han S, Zhao S. Comparative gene expression analysis of lymphocytes treated with exosomes derived from ovarian cancer and ovarian cysts. Front Immunol. 2017;8:607.PubMedPubMedCentralCrossRef
20.
Wei M, Yang T, Chen X, Wu Y, Deng X, He W, Yang J, Wang Z. Malignant ascites-derived exosomes promote proliferation and induce carcinoma-associated fibroblasts transition in peritoneal mesothelial cells. Oncotarget. 2017;
21.
ELA S, Mager I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12:347–57.CrossRef
22.
23.
CY W, SL D, Zhang J, Liang AL, Liu YJ. Exosomes and breast cancer: a comprehensive review of novel therapeutic strategies from diagnosis to treatment. Cancer Gene Ther. 2017;24:6–12.CrossRef
24.
Yang N, Li S, Li G, Zhang S, Tang X, Ni S, Jian X, Xu C, Zhu J, Lu M. The role of extracellular vesicles in mediating progression, metastasis and potential treatment of hepatocellular carcinoma. Oncotarget. 2017;8:3683–95.PubMed
25.
Li J, Yang X, Guan H, Mizokami A, Keller ET, Xu X, Liu X, Tan J, Hu L, Lu Y, Zhang J. Exosome-derived microRNAs contribute to prostate cancer chemoresistance. Int J Oncol. 2016;49:838–46.PubMed
26.
Jin H, Wu Y, Tan X. The role of pancreatic cancer-derived exosomes in cancer progress and their potential application as biomarkers. Clin Transl Oncol. 2017;19(8):921–30.PubMedCrossRef
27.
Webber J, Yeung V, Clayton A. Extracellular vesicles as modulators of the cancer microenvironment. Semin Cell Dev Biol. 2015;40:27–34.PubMedCrossRef
28.
Nedaeinia R, Manian M, Jazayeri MH, Ranjbar M, Salehi R, Sharifi M, Mohaghegh F, Goli M, Jahednia SH, Avan A, Ghayour-Mobarhan M. Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer. Cancer Gene Ther. 2017;24:48–56.PubMedCrossRef
29.
30.
Kowal J, Tkach M, Thery C. Biogenesis and secretion of exosomes. Curr Opin Cell Biol. 2014;29:116–25.PubMedCrossRef
31.
Gross JC, Chaudhary V, Bartscherer K, Boutros M. Active Wnt proteins are secreted on exosomes. Nat Cell Biol. 2012;14:1036–45.PubMedCrossRef
32.
Savina A, Furlan M, Vidal M, Colombo MI. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem. 2003;278:20083–90.PubMedCrossRef
33.
Li J, Yu J, Liu A, Wang Y. Retraction notice to "ss-elemene against human lung cancer via up-regulation of P53 protein expression to promote the release of exosome": LUNG 86/2 (2014) 144-150. Lung Cancer. 2016;96:120.PubMedCrossRef
34.
Thompson CA, Purushothaman A, Ramani VC, Vlodavsky I, Sanderson RD. Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes. J Biol Chem. 2013;288:10093–9.PubMedPubMedCentralCrossRef
35.
Aubertin K, Silva AK, Luciani N, Espinosa A, Djemat A, Charue D, Gallet F, Blanc-Brude O, Wilhelm C. Massive release of extracellular vesicles from cancer cells after photodynamic treatment or chemotherapy. Sci Rep. 2016;6:35376.PubMedPubMedCentralCrossRef
36.
Tian T, Wang Y, Wang H, Zhu Z, Xiao Z. Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy. J Cell Biochem. 2010;111:488–96.PubMedCrossRef
37.
Feng D, Zhao WL, Ye YY, Bai XC, Liu RQ, Chang LF, Zhou Q, Sui SF. Cellular internalization of exosomes occurs through phagocytosis. Traffic. 2010;11:675–87.PubMedCrossRef
38.
39.
Witwer KW, Buzas EI, Bemis LT, Bora A, Lasser C, Lotvall J, Nolte-'t Hoen EN, Piper MG, Sivaraman S, Skog J, Thery C, Wauben MH, Hochberg F. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles. 2013;2:1–25.
40.
Xu R, Greening DW, Zhu HJ, Takahashi N, Simpson RJ. Extracellular vesicle isolation and characterization: toward clinical application. J Clin Invest. 2016;126:1152–62.PubMedPubMedCentralCrossRef
41.
Ko J, Carpenter E, Issadore D. Detection and isolation of circulating exosomes and microvesicles for cancer monitoring and diagnostics using micro−/nano-based devices. Analyst. 2016;141:450–60.PubMedPubMedCentralCrossRef
42.
Erdbrugger U, Lannigan J. Analytical challenges of extracellular vesicle detection: a comparison of different techniques. Cytometry A. 2016;89:123–34.PubMedCrossRef
43.
Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 1820;2012:940–8.
44.
Liang B, Peng P, Chen S, Li L, Zhang M, Cao D, Yang J, Li H, Gui T, Li X, Shen K. Characterization and proteomic analysis of ovarian cancer-derived exosomes. J Proteome. 2013;80:171–82.CrossRef
45.
Zhan HX, Zhou B, Cheng YG, JW X, Wang L, Zhang GY, Crosstalk HSY. Between stromal cells and cancer cells in pancreatic cancer: new insights into stromal biology. Cancer Lett. 2017;392:83–93.PubMedCrossRef
46.
47.
Allinen M, Beroukhim R, Cai L, Brennan C, Lahti-Domenici J, Huang H, Porter D, Hu M, Chin L, Richardson A, Schnitt S, Sellers WR, Polyak K. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell. 2004;6:17–32.PubMedCrossRef
48.
49.
Zhao H, Yang L, Baddour J, Achreja A, Bernard V, Moss T, Marini JC, Tudawe T, Seviour EG, San Lucas FA, Alvarez H, Gupta S, Maiti SN, et al. Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism. elife. 2016;5:e10250.PubMedPubMedCentral
50.
Brauer HA, Makowski L, Hoadley KA, Casbas-Hernandez P, Lang LJ, Roman-Perez E, D'Arcy M, Freemerman AJ, Perou CM, Troester MA. Impact of tumor microenvironment and epithelial phenotypes on metabolism in breast cancer. Clin Cancer Res. 2013;19:571–85.PubMedCrossRef
51.
Luga V, Zhang L, Viloria-Petit AM, Ogunjimi AA, Inanlou MR, Chiu E, Buchanan M, Hosein AN, Basik M, Wrana JL. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell. 2012;151:1542–56.PubMedCrossRef
52.
Boelens MC, TJ W, Nabet BY, Xu B, Qiu Y, Yoon T, Azzam DJ, Twyman-Saint Victor C, Wiemann BZ, Ishwaran H, Ter Brugge PJ, Jonkers J, Slingerland J, et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell. 2014;159:499–513.PubMedPubMedCentralCrossRef
53.
Pang W, Su J, Wang Y, Feng H, Dai X, Yuan Y, Chen X, Yao W. Pancreatic cancer-secreted miR-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts. Cancer Sci. 2015;106:1362–9.PubMedPubMedCentralCrossRef
54.
Richards KE, Zeleniak AE, Fishel ML, Wu J, Littlepage LE, Hill R. Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene. 2017;36:1770–8.PubMedCrossRef
55.
Ristorcelli E, Beraud E, Verrando P, Villard C, Lafitte D, Sbarra V, Lombardo D, Verine A. Human tumor nanoparticles induce apoptosis of pancreatic cancer cells. FASEB J. 2008;22:3358–69.PubMedCrossRef
56.
Ristorcelli E, Beraud E, Mathieu S, Lombardo D, Verine A. Essential role of notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles. Int J Cancer. 2009;125:1016–26.PubMedCrossRef
57.
Schneider J, Chromik AM, Uhl W, Mugge A, Bulut D. Apoptosis in esophagus and pancreas carcinoma cells induced by circulating microparticles is related to phosphatidyl serine and microparticle-associated caspases. Med Oncol. 2012;29:962–9.PubMedCrossRef
58.
Takikawa T, Masamune A, Yoshida N, Hamada S, Kogure T, Shimosegawa T. Exosomes derived from pancreatic stellate cells: MicroRNA signature and effects on pancreatic cancer cells. Pancreas. 2017;46:19–27.PubMedCrossRef
59.
Leca J, Martinez S, Lac S, Nigri J, Secq V, Rubis M, Bressy C, Serge A, Lavaut MN, Dusetti N, Loncle C, Roques J, Pietrasz D, et al. Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. J Clin Invest. 2016;126:4140–56.PubMedPubMedCentralCrossRef
60.
Gamperl H, Plattfaut C, Freund A, Quecke T, Theophil F, Gieseler F. Extracellular vesicles from malignant effusions induce tumor cell migration: inhibitory effect of LMWH tinzaparin. Cell Biol Int. 2016;40:1050–61.PubMedCrossRef
61.
Jung T, Castellana D, Klingbeil P, Hernández IC, Vitacolonna M, Orlicky DJ, Roffler SR, Brodt P, Zöller M. CD44v6 dependence of Premetastatic niche preparation by exosomes. Neoplasia. 2009;11:1093–IN17.PubMedPubMedCentralCrossRef
62.
Wang Z, Von Au A, Schnolzer M, Hackert T, Zoller M. CD44v6-competent tumor exosomes promote motility, invasion and cancer-initiating cell marker expression in pancreatic and colorectal cancer cells. Oncotarget. 2016;7:55409–36.PubMedPubMedCentralCrossRef
63.
64.
Yue S, Mu W, Erb U, Zoller M. The tetraspanins CD151 and Tspan8 are essential exosome components for the crosstalk between cancer initiating cells and their surrounding. Oncotarget. 2015;6:2366–84.PubMedCrossRef
65.
66.
67.
Song X, Ding Y, Liu G, Yang X, Zhao R, Zhang Y, Zhao X, Anderson GJ, Nie G. Cancer cell-derived exosomes induce mitogen-activated protein kinase-dependent monocyte survival by transport of functional receptor tyrosine kinases. J Biol Chem. 2016;291:8453–64.PubMedPubMedCentralCrossRef
68.
Javeed N, Gustafson MP, Dutta SK, Lin Y, Bamlet WR, Oberg AL, Petersen GM, Chari ST, Dietz AB, Mukhopadhyay D. Immunosuppressive CD14+HLA-DRlo/neg monocytes are elevated in pancreatic cancer and "primed" by tumor-derived exosomes. Oncoimmunology 2017; 6: e1252013.
69.
Katsiougiannis S, Chia D, Kim Y, Singh RP, Wong DT. Saliva exosomes from pancreatic tumor-bearing mice modulate NK cell phenotype and antitumor cytotoxicity. FASEB J. 2017;31:998–1010.PubMedCrossRef
70.
Ding G, Zhou L, Qian Y, Fu M, Chen J, Chen J, Xiang J, Wu Z, Jiang G, Cao L. Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p. Oncotarget. 2015;6:29877–88.PubMedPubMedCentralCrossRef
71.
Zhou M, Chen J, Zhou L, Chen W, Ding G, Cao L. Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203. Cell Immunol. 2014;292:65–9.PubMedCrossRef
72.
Que RS, Lin C, Ding GP, Wu ZR, Cao LP. Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer. J Zhejiang Univ Sci B. 2016;17:352–60.PubMedPubMedCentralCrossRef
73.
Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 2005;65:5238–47.PubMedPubMedCentralCrossRef
74.
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.PubMedCrossRef
75.
Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zulke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310:1473–81.PubMedCrossRef
76.
Maeda A, Boku N, Fukutomi A, Kondo S, Kinoshita T, Nagino M, Uesaka K. Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 in patients with resected pancreatic cancer: Japan adjuvant study Group of Pancreatic Cancer (JASPAC-01). Jpn J Clin Oncol. 2008;38:227–9.PubMedCrossRef
77.
Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 2007;25:1960–6.PubMedCrossRef
78.
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.PubMedPubMedCentralCrossRef
79.
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.PubMedCrossRef
80.
Crompot E, Van Damme M, Pieters K, Vermeersch M, Perez-Morga D, Mineur P, Maerevoet M, Meuleman N, Bron D, Lagneaux L, Stamatopoulos B. Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B-cells from apoptosis, enhance their migration and induce gene expression modifications. Haematologica. 2017;
81.
Zeng AL, Yan W, Liu YW, Wang Z, Hu Q, Nie E, Zhou X, Li R, Wang XF, Jiang T, You YP. Tumour exosomes from cells harbouring PTPRZ1-MET fusion contribute to a malignant phenotype and temozolomide chemoresistance in glioblastoma. Oncogene. 2017;
82.
Lobb RJ, van Amerongen R, Wiegmans A, Ham S, Larsen JE, Moller A. Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance. Int J Cancer. 2017;141:614–20.PubMedCrossRef
83.
Zheng P, Chen L, Yuan X, Luo Q, Liu Y, Xie G, Ma Y, Shen L. Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells. J Exp Clin Cancer Res. 2017;36:53.PubMedPubMedCentralCrossRef
84.
Ning K, Wang T, Sun X, Zhang P, Chen Y, Jin J, Hua D. UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer. J Surg Oncol. 2017;115:932–40.PubMedCrossRef
85.
Au Yeung CL, Co NN, Tsuruga T, Yeung TL, Kwan SY, Leung CS, Li Y, Lu ES, Kwan K, Wong KK, Schmandt R, Lu KH, Mok SC. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun. 2016;7:11150.PubMedPubMedCentralCrossRef
86.
Wang X, Xu C, Hua Y, Sun L, Cheng K, Jia Z, Han Y, Dong J, Cui Y, Yang Z. Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer. J Exp Clin Cancer Res. 2016;35:186.PubMedPubMedCentralCrossRef
87.
Kreger BT, Johansen ER, Cerione RA, Antonyak MA. The enrichment of Survivin in exosomes from breast cancer cells treated with paclitaxel promotes cell survival and Chemoresistance. Cancers (Basel). 2016;8:1–14.
88.
Patel GK, Khan MA, Bhardwaj A, Srivastava SK, Zubair H, Patton MC, Singh S, Khushman M, Singh AP. Exosomes confer chemoresistance to pancreatic cancer cells by promoting ROS detoxification and miR-155-mediated suppression of key gemcitabine-metabolising enzyme, DCK. Br J Cancer. 2017;116:609–19.PubMedCrossRef
89.
Santos JC, Ribeiro ML, Sarian LO, Ortega MM, Derchain SF. Exosomes-mediate microRNAs transfer in breast cancer chemoresistance regulation. Am J Cancer Res. 2016;6:2129–39.PubMedPubMedCentral
90.
Namba T, Kodama R, Moritomo S, Hoshino T, Mizushima T. Zidovudine, an anti-viral drug, resensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine by inhibition of the Akt-GSK3beta-snail pathway. Cell Death Dis. 2015;6:e1795.PubMedPubMedCentralCrossRef
91.
Khorana AA, Mangu PB, Berlin J, Engebretson A, Hong TS, Maitra A, Mohile SG, Mumber M, Schulick R, Shapiro M, Urba S, Zeh HJ, Katz MH. Potentially curable pancreatic cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2016;34:2541–56.PubMedCrossRef
92.
Zhan HX, JW X, Wu D, Zhang TP, Pancreatic HSY. Cancer stem cells: new insight into a stubborn disease. Cancer Lett. 2015;357:429–37.PubMedCrossRef
93.
Egawa S, Toma H, Ohigashi H, Okusaka T, Nakao A, Hatori T, Maguchi H, Yanagisawa A, Tanaka M. Japan pancreatic cancer registry; 30th year anniversary: Japan pancreas society. Pancreas. 2012;41:985–92.PubMedCrossRef
94.
95.
Goonetilleke KS, Siriwardena AK. Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer. Eur J Surg Oncol. 2007;33:266–70.PubMedCrossRef
96.
Ciardiello C, Cavallini L, Spinelli C, Yang J, Reis-Sobreiro M, de Candia P, Minciacchi VR, Di Vizio D. Focus on extracellular vesicles: new Frontiers of cell-to-cell communication in cancer. Int J Mol Sci. 2016;17:175.PubMedPubMedCentralCrossRef
97.
Erb U, Zoller M. Progress and potential of exosome analysis for early pancreatic cancer detection. Expert Rev Mol Diagn. 2016;16:757–67.PubMedCrossRef
98.
Que R, Ding G, Chen J, Cao L. Analysis of serum exosomal microRNAs and clinicopathologic features of patients with pancreatic adenocarcinoma. World J Surg Oncol. 2013;11:219.PubMedPubMedCentralCrossRef
99.
Taller D, Richards K, Slouka Z, Senapati S, Hill R, Go DB, Chang HC. On-chip surface acoustic wave lysis and ion-exchange nanomembrane detection of exosomal RNA for pancreatic cancer study and diagnosis. Lab Chip. 2015;15:1656–66.PubMedCrossRef
100.
Joshi GK, Deitz-McElyea S, Liyanage T, Lawrence K, Mali S, Sardar R, Korc M. Label-free Nanoplasmonic-based short noncoding RNA sensing at Attomolar concentrations allows for quantitative and highly specific assay of MicroRNA-10b in biological fluids and circulating exosomes. ACS Nano. 2015;9:11075–89.PubMedPubMedCentralCrossRef
101.
Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J, LeBleu VS, Mittendorf EA, Weitz J, Rahbari N, Reissfelder C, Pilarsky C, Fraga MF, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523:177–82.PubMedPubMedCentralCrossRef
102.
Lai X, Wang M, McElyea SD, Sherman S, House M, Korc MA. microRNA signature in circulating exosomes is superior to exosomal glypican-1 levels for diagnosing pancreatic cancer. Cancer Lett. 2017;393:86–93.PubMedPubMedCentralCrossRef
103.
Madhavan B, Yue S, Galli U, Rana S, Gross W, Muller M, Giese NA, Kalthoff H, Becker T, Buchler MW, Zoller M. Combined evaluation of a panel of protein and miRNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity. Int J Cancer. 2015;136:2616–27.PubMedCrossRef
104.
Bahn JH, Zhang Q, Li F, Chan TM, Lin X, Kim Y, Wong DT, Xiao X. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem. 2015;61:221–30.PubMedCrossRef
105.
Machida T, Tomofuji T, Maruyama T, Yoneda T, Ekuni D, Azuma T, Miyai H, Mizuno H, Kato H, Tsutsumi K, Uchida D, Takaki A, Okada H, et al. miR1246 and miR4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer. Oncol Rep. 2016;36:2375–81.PubMedCrossRef
106.
Lau C, Kim Y, Chia D, Spielmann N, Eibl G, Elashoff D, Wei F, Lin YL, Moro A, Grogan T, Chiang S, Feinstein E, Schafer C, et al. Role of pancreatic cancer-derived exosomes in salivary biomarker development. J Biol Chem. 2013;288:26888–97.PubMedPubMedCentralCrossRef
107.
Kanwar SS, Dunlay CJ, Simeone DM, Nagrath S. Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab Chip. 2014;14:1891–900.PubMedPubMedCentralCrossRef
108.
Tkach M, Kowal J, Zucchetti AE, Enserink L, Jouve M, Lankar D, Saitakis M, Martin-Jaular L, Thery C. Qualitative differences in T-cell activation by dendritic cell-derived extracellular vesicle subtypes. EMBO J. 2017;36(20):3012–28.PubMedCrossRef
109.
Chen W, Wang J, Shao C, Liu S, Yu Y, Wang Q, Cao X. Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells. Eur J Immunol. 2006;36:1598–607.PubMedCrossRef
110.
Rao Q, Zuo B, Lu Z, Gao X, You A, Wu C, Du Z, Yin H. Tumor-derived exosomes elicit tumor suppression in murine hepatocellular carcinoma models and humans in vitro. Hepatology. 2016;64:456–72.PubMedCrossRef
111.
Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H, Li G, Phase I. Clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther. 2008;16:782–90.PubMedCrossRef
112.
Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, Valente N, Shreeniwas R, Sutton MA, Delcayre A, Hsu DH, Le Pecq JB, Lyerly HKA. Phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3:9.PubMedPubMedCentralCrossRef
113.
Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M. A comprehensive overview of exosomes as drug delivery vehicles - endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta. 1846;2014:75–87.
114.
Vader P, Mol EA, Pasterkamp G, Schiffelers RM. Extracellular vesicles for drug delivery. Adv Drug Deliv Rev. 2016;106:148–56.PubMedCrossRef
115.
Pascucci L, Cocce V, Bonomi A, Ami D, Ceccarelli P, Ciusani E, Vigano L, Locatelli A, Sisto F, Doglia SM, Parati E, Bernardo ME, Muraca M, 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.PubMedCrossRef
116.
Osterman CJ, Lynch JC, Leaf P, Gonda A, Ferguson Bennit HR, Griffiths D, Wall NR. Curcumin modulates pancreatic adenocarcinoma cell-derived Exosomal function. PLoS One. 2015;10:e0132845.PubMedPubMedCentralCrossRef
117.
Kamerkar S, LeBleu VS, Sugimoto H, Yang S, Ruivo CF, Melo SA, Lee JJ, Kalluri R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017;546:498–503.PubMedPubMedCentral
118.
Aspe JR, Diaz Osterman CJ, Jutzy JM, Deshields S, Whang S, Wall NR. Enhancement of gemcitabine sensitivity in pancreatic adenocarcinoma by novel exosome-mediated delivery of the Survivin-T34A mutant. J Extracell Vesicles. 2014;3:1–9.
119.
Mahmoodzadeh Hosseini H, Ali Imani Fooladi A, Soleimanirad J, Reza Nourani M, Mahdavi M. Exosome/staphylococcal enterotoxin B, an anti tumor compound against pancreatic cancer. J buon. 2014;19:440–8.PubMed
120.
Metadata
Title
Extracellular vesicles as mediators of the progression and chemoresistance of pancreatic cancer and their potential clinical applications
Authors
Jiangdong Qiu
Gang Yang
Mengyu Feng
Suli Zheng
Zhe Cao
Lei You
Lianfang Zheng
Taiping Zhang
Yupei Zhao
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2018
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-017-0755-z

Other articles of this Issue 1/2018

Molecular Cancer 1/2018 Go to the issue

Review

Deciphering mechanisms of brain metastasis in melanoma - the gist of the matter

Review

Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma

Letter to the Editor

EphB2 stem-related and EphA2 progression-related miRNA-based networks in progressive stages of CRC evolution: clinical significance and potential miRNA drivers

Review

Expression, regulation and targeting of receptor tyrosine kinases in esophageal squamous cell carcinoma

Research

CCL2/CCL5 secreted by the stroma induce IL-6/PYK2 dependent chemoresistance in ovarian cancer

Review

PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits