New insights in the composition of extracellular vesicles from pancreatic cancer cells: implications for biomarkers and functions
Tóm tắt
Pancreatic cancer development is associated with characteristic alterations like desmoplastic reaction and immune escape which are mediated by the cell-cell communication mechanism and by the microenvironment of the cells. The whole of released components are important determinants in these processes. Especially the extracellular vesicles released by pancreatic cancer cells play a role in cell communication and modulate cell growth and immune responses. Here, we present the proteomic description of affinity purified extracellular vesicles from pancreatic tumour cells, compared to the secretome, defined as the whole of the proteins released by pancreatic cancer cells. The proteomic data provide comprehensive catalogues of hundreds of proteins, and the comparison reveals a special proteomic composition of pancreatic cancer cell derived extracellular vesicles. The functional analysis of the protein composition displayed that membrane proteins, glycoproteins, small GTP binding proteins and a further, heterogeneous group of proteins are enriched in vesicles, whereas proteins derived from proteasomes and ribosomes, as well as metabolic enzymes, are not components of the vesicles. Furthermore proteins playing a role in carcinogenesis and modulators of the extracellular matrix (ECM) or cell-cell interactions are components of affinity purified extracellular vesicles. The data deepen the knowledge of extracellular vesicle composition by hundreds of proteins that have not been previously described as vesicle components released by pancreatic cancer cells. Extracellular vesicles derived from pancreatic cancer cells show common proteins shared with other vesicles as well as cell type specific proteins indicating biomarker candidates and suggesting functional roles in cancer cell stroma interactions.
Tài liệu tham khảo
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, Forman D, Bray F: Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013, 49: 1374–1403. 10.1016/j.ejca.2012.12.027
Gukovsky I, Li N, Todoric J, Gukovskaya A, Karin M: Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology 2013, 144: 1199–1209. e4 10.1053/j.gastro.2013.02.007
Shah MM, Saif MW: Pancreatic cancer and thrombosis. highlights from the "2010 ASCO Annual Meeting". Chicago, IL, USA. June 4-8, 2010. JOP 2010, 11: 331–333.
Caccia D, Zanetti Domingues L, Micciché F, de Bortoli M, Carniti C, Mondellini P, Bongarzone I: Secretome compartment is a valuable source of biomarkers for cancer-relevant pathways. J Proteome Res 2011, 10: 4196–4207. 10.1021/pr200344n
Cocucci E, Racchetti G, Meldolesi J: Shedding microvesicles: artefacts no more. Trends Cell Biol 2009, 19: 43–51. 10.1016/j.tcb.2008.11.003
Choi D, Lee J, Go G, Kim Y, Gho YS: Circulating extracellular vesicles in cancer diagnosis and monitoring: an appraisal of clinical potential. Mol Diagn Ther 2013, 17: 265–271. 10.1007/s40291-013-0042-7
Webber J, Clayton A: How pure are your vesicles? J Extracell Vesicles 2013, 2: 19861. 10.3402/jev.v2i0.19861
Muralidharan-Chari V, Clancy JW, Sedgwick A, D'Souza-Schorey C: Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 2010, 123: 1603–1611. 10.1242/jcs.064386
D'Souza-Schorey C, Clancy JW: Tumor-derived microvesicles: shedding light on novel microenvironment modulators and prospective cancer biomarkers. Genes Dev 2012, 26: 1287–1299. 10.1101/gad.192351.112
Raposo G, Stoorvogel W: Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 2013, 200: 373–383. 10.1083/jcb.201211138
Chaput N, Théry C: Exosomes: immune properties and potential clinical implementations. Semin Immunopathol 2011, 33: 419–440. 10.1007/s00281-010-0233-9
Henderson MC, Azorsa DO: The genomic and proteomic content of cancer cell-derived exosomes. Front Oncol 2012, 2: 38. 10.3389/fonc.2012.00038
Bang C, Thum T: Exosomes: new players in cell-cell communication. Int J Biochem Cell Biol 2012, 44: 2060–2064. 10.1016/j.biocel.2012.08.007
Garcia-Contreras M, Ricordi C, Robbins PD, Oltra E: Exosomes in the pathogenesis, diagnosis and treatment of pancreatic diseases. CellR4 2014, 2: e807.
Mathivanan S, Fahner CJ, Reid GE, Simpson RJ: ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res 2012, 40: D1241-D1244. 10.1093/nar/gkr828
Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ: B lymphocytes secrete antigen-presenting vesicles. J Exp Med 1996, 183: 1161–1172. 10.1084/jem.183.3.1161
Mathivanan S, Lim JW, Tauro BJ, Ji H, Moritz RL, Simpson RJ: Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol Cell Proteomics 2010, 9: 197–208. 10.1074/mcp.M900152-MCP200
Choi D, Kim D, Kim Y, Gho YS: Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics 2013, 13: 1554–1571. 10.1002/pmic.201200329
Cirulli V, Crisa L, Beattie GM, Mally MI, Lopez AD, Fannon A, Ptasznik A, Inverardi L, Ricordi C, Deerinck T, Ellisman M, Reisfeld RA, Hayek A: KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells: morphoregulatory roles in pancreatic islet development. J Cell Biol 1998, 140: 1519–1534. 10.1083/jcb.140.6.1519
Moore PS, Sipos B, Orlandini S, Sorio C, Real FX, Lemoine NR, Gress T, Bassi C, Kloppel G, Kalthoff H, Ungefroren H, Lohr M, Scarpa A: Genetic profile of 22 pancreatic carcinoma cell lines. analysis of K-ras, p53, p16 and DPC4/Smad4. Virchows Arch 2001, 439: 798–802. 10.1007/s004280100474
Jansen FH, Krijgsveld J, van Rijswijk A, van den Bemd G-J, van den Berg MS, van Weerden WM, Willemsen R, Dekker LJ, Luider TM, Jenster G: Exosomal secretion of cytoplasmic prostate cancer xenograft-derived proteins. Mol Cell Proteomics 2009, 8: 1192–1205. 10.1074/mcp.M800443-MCP200
Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, Bond VC, Borrás FE, Breakefield X, Budnik V, Buzas E, Camussi G, Clayton A, Cocucci E, Falcon-Perez JM, Gabrielsson S, Gho YS, Gupta D, Harsha HC, Hendrix A, Hill AF, Inal JM, Jenster G, Krämer-Albers E, Lim SK, Llorente A, Lötvall J, Marcilla A, Mincheva-Nilsson L, Nazarenko I, et al.: Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol 2012, 10: e1001450. 10.1371/journal.pbio.1001450
Kuo L, Freed EO: ARRDC1 as a mediator of microvesicle budding. Proc Natl Acad Sci U S A 2012, 109: 4025–4026. 10.1073/pnas.1201441109
Nabhan JF, Hu R, Oh RS, Cohen SN, Lu Q: Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc Natl Acad Sci U S A 2012, 109: 4146–4151. 10.1073/pnas.1200448109
Chelala C, Hahn SA, Whiteman HJ, Barry S, Hariharan D, Radon TP, Lemoine NR, Crnogorac-Jurcevic T: Pancreatic expression database: a generic model for the organization, integration and mining of complex cancer datasets. BMC Genomics 2007, 8: 439. 10.1186/1471-2164-8-439
Erkan M: Antifibrotic therapy in pancreatic diseases. Gut 2013, 62: 1244–1245. 10.1136/gutjnl-2012-303937
Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L: Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 2001, 7: 297–303. 10.1038/85438
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: 654–659. 10.1038/ncb1596
Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO: Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 2008, 10: 1470–1476. 10.1038/ncb1800
Colombo M, Moita C, Van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, Moita LF, Théry C, Raposo G: Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci 2013, 126: 5553–5565. 10.1242/jcs.128868
Gress TM, Menke A, Bachem MG, Muller-Pillasch F, Ellenrieder V, Weidenbach H, Wagner M, Adler G: Role of extracellular matrix in pancreatic diseases. Digestion 1998, 59: 625–637. 10.1159/000007567
Tauro BJ, Greening DW, Mathias RA, Mathivanan S, Ji H, Simpson RJ: Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol Cell Proteomics 2013, 12: 587–598. 10.1074/mcp.M112.021303
Donaldson JG, Jackson CL: ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol 2011, 12: 362–375. 10.1038/nrm3117
Lau C, Kim Y, Chia D, Spielmann N, Eibl G, Elashoff D, Wei F, Lin Y, Moro A, Grogan T, Chiang S, Feinstein E, Schafer C, Farrell J, Wong DTW: Role of pancreatic cancer-derived exosomes in salivary biomarker development. J Biol Chem 2013, 288: 26888–26897. 10.1074/jbc.M113.452458
Mu W, Rana S, Zöller M: Host matrix modulation by tumor exosomes promotes motility and invasiveness. Neoplasia 2013, 15: 875–887.
Sleeman JP: The metastatic niche and stromal progression. Cancer Metastasis Rev 2012, 31: 429–440. 10.1007/s10555-012-9373-9
Iacono KT, Brown AL, Greene MI, Saouaf SJ: CD147 immunoglobulin superfamily receptor function and role in pathology. Exp Mol Pathol 2007, 83: 283–295. 10.1016/j.yexmp.2007.08.014
Gao W, Chen L, Ma Z, Du Z, Zhao Z, Hu Z, Li Q: Isolation and phenotypic characterization of colorectal cancer stem cells with organ-specific metastatic potential. Gastroenterology 2013, 145: 636–646. e5 10.1053/j.gastro.2013.05.049
Adamczyk KA, Klein-Scory S, Tehrani MM, Warnken U, Schmiegel W, Schnölzer M, Schwarte-Waldhoff I: Characterization of soluble and exosomal forms of the EGFR released from pancreatic cancer cells. Life Sci 2011, 89: 304–312. 10.1016/j.lfs.2011.06.020
Valenti R, Huber V, Iero M, Filipazzi P, Parmiani G, Rivoltini L: Tumor-released microvesicles as vehicles of immunosuppression. Cancer Res 2007, 67: 2912–2915. 10.1158/0008-5472.CAN-07-0520
Corrado C, Raimondo S, Chiesi A, Ciccia F, Leo de G, Alessandro R: Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int J Mol Sci 2013, 14: 5338–5366. 10.3390/ijms14035338
Clayton A, Al-Taei S, Webber J, Mason MD, Tabi Z: Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production. J Immunol 2011, 187: 676–683. 10.4049/jimmunol.1003884
Beavis PA, Stagg J, Darcy PK, Smyth MJ: CD73: a potent suppressor of antitumor immune responses. Trends Immunol 2012, 33: 231–237. 10.1016/j.it.2012.02.009
Taylor DD, Gercel-Taylor C: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 2008, 110: 13–21. 10.1016/j.ygyno.2008.04.033
Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM, Simpson RJ: Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 2012, 56: 293–304. 10.1016/j.ymeth.2012.01.002
Rupp A, Rupp C, Keller S, Brase JC, Ehehalt R, Fogel M, Moldenhauer G, Marmé F, Sültmann H, Altevogt P: Loss of EpCAM expression in breast cancer derived serum exosomes: role of proteolytic cleavage. Gynecol Oncol 2011, 122: 437–446. 10.1016/j.ygyno.2011.04.035
Wu X, He X, Chen Y, Yuan R, Zeng Y, Lian L, Zou Y, Lan N, Wu X, Lan P: High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. J Surg Oncol 2012, 106: 130–137. 10.1002/jso.23056
van Niel G, Raposo G, Candalh C, Boussac M, Hershberg R, Cerf-Bensussan N, Heyman M: Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 2001, 121: 337–349. 10.1053/gast.2001.26263
Taylor DD, Zacharias W, Gercel-Taylor C: Exosome isolation for proteomic analyses and RNA profiling. Methods Mol Biol 2011, 728: 235–246. 10.1007/978-1-61779-068-3_15
Battke C, Ruiss R, Welsch U, Wimberger P, Lang S, Jochum S, Zeidler R: Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol Immunother 2011, 60: 639–648. 10.1007/s00262-011-0979-5
Liu C, Yu S, Zinn K, Wang J, Zhang L, Jia Y, Kappes JC, Barnes S, Kimberly RP, Grizzle WE, Zhang H: Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol 2006, 176: 1375–1385. 10.4049/jimmunol.176.3.1375
Piersma SR, Fiedler U, Span S, Lingnau A, Pham TV, Hoffmann S, Kubbutat MHG, Jiménez CR: Workflow comparison for label-free, quantitative secretome proteomics for cancer biomarker discovery: method evaluation, differential analysis, and verification in serum. J Proteome Res 2010, 9: 1913–1922. 10.1021/pr901072h
Huang DW, Sherman BT, RA: Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources. DAVID Bioinformatics Resources.Nat Protoc 2009, 57:44-57., [Lempicki]
Chen J, Bardes EE, Aronow BJ, Jegga AG: ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 2009, 37: W305. 10.1093/nar/gkp427