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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2015

Open Access 01-12-2015 | Research

Proteomic analysis of exosomes derived from human lymphoma cells

Authors: Ye Yao, Wei Wei, Jing Sun, Linjun Chen, Xiaohui Deng, Liyuan Ma, Siguo Hao

Published in: European Journal of Medical Research | Issue 1/2015

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Abstract

Background

Exosomes secreted by tumor cells contain specific antigens that may have immunotherapeutic purposes. The aim of this study was to characterize the proteomic content of lymphoma cell-derived exosomes (LCEXs).

Methods

In this study, exosomes derived from Raji cells (EXORaji) were purified and proteins of EXORaji were separated by one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein bands were identified by mass spectrometry. The protein components of EXORaji were analyzed using shotgun technology, and the function proteins of EXORaji were defined and described using the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

Results

A total of 197 proteins were identified in EXORaji; 139 proteins were also identified in Raji cells, showing an overlap of 70.56% of the total proteins in EXORaji. Interestingly, the remaining 58 proteins were unique to EXORaji. The GO database and KEGG were used to define and describe the function of proteins. The data showed that some important proteins involved in antigen procession and presentation as well as cell migration and adhesion were also identified in EXORaji, such as MHC-I and II, HSC70, HSP90, and ICMA-1.

Conclusions

LCEXs express a discrete set of proteins involved in antigen presentation and cell migration and adhesion, suggesting that LCEXs play an important role in the regulation of immunity and interaction between lymphoma cells and their microenvironment. LCEXs harbor most of the proteins of lymphoma cells and could be one of the sources of lymphoma-associated antigens for immunotherapeutic purposes.
Literature
1.
Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci. 2000;113(Pt 19):3365–74.PubMed
2.
Ge R, Tan E, Sharghi-Namini S, Asada HH. Exosomes in the cancer microenvironment and beyond: have we overlooked these extracellular messengers? Cancer Microenviron. 2012;5(3):323–32.CrossRefPubMedCentralPubMed
3.
4.
Kharaziha P, Ceder S, Li Q, Panaretakis T. Tumor cell-derived exosomes: a message in a bottle. Biochim Biophys Acta. 2012;1826(1):103–11.PubMed
5.
Hao S, Bai O, Li F, Yuan J, Laferte S, Xiang J. Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumour immunity. Immunology. 2007;120(1):90–102.CrossRefPubMedCentralPubMed
6.
Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, et al. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol. 2001;166(12):7309–18.CrossRefPubMed
7.
Thery C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, et al. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999;147(3):599–610.CrossRefPubMedCentralPubMed
8.
Andre F, Schartz NE, Movassagh M, Flament C, Pautier P, Morice P, et al. Malignant effusions and immunogenic tumour-derived exosomes. Lancet. 2002;360(9329):295–305.CrossRefPubMed
9.
Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001;7(3):297–303.CrossRefPubMed
10.
Yao Y, Chen L, Wei W, Deng X, Ma L, Hao S. Tumor cell-derived exosome-targeted dendritic cells stimulate stronger CD8+ CTL responses and antitumor immunities. Biochem Biophys Res Commun. 2013;436(1):60–5.CrossRefPubMed
11.
San Miguel JF, Martinez A, Macedo A, Vidriales MB, Lopez-Berges C, Gonzalez M, et al. Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood. 1997;90(6):2465–70.PubMed
12.
Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta. 2012;1820(7):940–8.CrossRefPubMed
13.
Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010;116(19):3724–34.CrossRefPubMed
14.
Shen C, Hao SG, Zhao CX, Zhu J, Wang C. Antileukaemia immunity: effect of exosomes against NB4 acute promyelocytic leukaemia cells. J Int Med Res. 2011;39(3):740–7.CrossRefPubMed
15.
Merchant ML, Powell DW, Wilkey DW, Cummins TD, Deegens JK, Rood IM, et al. Microfiltration isolation of human urinary exosomes for characterization by MS. Proteomics Clin Appl. 2010;4(1):84–96.CrossRefPubMed
16.
17.
Yao Y, Wang C, Wei W, Shen C, Deng X, Chen L, et al. Dendritic cells pulsed with leukemia cell-derived exosomes more efficiently induce antileukemic immunities. PLoS One. 2014;9(3):e91463.CrossRefPubMedCentralPubMed
18.
Andre F, Chaput N, Schartz NE, Flament C, Aubert N, Bernard J, et al. Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol. J Immunol. 2004;172(4):2126–36.CrossRefPubMed
19.
Andre F, Schartz NE, Chaput N, Flament C, Raposo G, Amigorena S, et al. Tumor-derived exosomes: a new source of tumor rejection antigens. Vaccine. 2002;20 Suppl 4:A28–31.CrossRefPubMed
20.
21.
Castellanos A, Pintado B, Weruaga E, Arevalo R, Lopez A, Orfao A, et al. A BCR-ABL(p190) fusion gene made by homologous recombination causes B-cell acute lymphoblastic leukemias in chimeric mice with independence of the endogenous bcr product. Blood. 1997;90(6):2168–74.PubMed
22.
Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106(7):1569–80.CrossRefPubMed
23.
Hao S, Bai O, Yuan J, Qureshi M, Xiang J. Dendritic cell-derived exosomes stimulate stronger CD8+ CTL responses and antitumor immunity than tumor cell-derived exosomes. Cell Mol Immunol. 2006;3(3):205–11.PubMed
24.
Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Hoyer-Hansen M, et al. Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med. 2004;200(4):425–35.CrossRefPubMedCentralPubMed
25.
Pockley AG. Heat shock proteins in health and disease: therapeutic targets or therapeutic agents? Expert Rev Mol Med. 2001;3(23):1–21.CrossRefPubMed
26.
27.
Young D, Roman E, Moreno C, O'Brien R, Born W. Molecular chaperones and the immune response. Philos Trans R Soc Lond B Biol Sci. 1993;339(1289):363–7. Discussion 367–368.CrossRefPubMed
28.
Arnold-Schild D, Hanau D, Spehner D, Schmid C, Rammensee HG, de la Salle H, et al. Cutting edge: receptor-mediated endocytosis of heat shock proteins by professional antigen-presenting cells. J Immunol. 1999;162(7):3757–60.PubMed
29.
Binder RJ, Han DK, Srivastava PK. CD91: a receptor for heat shock protein gp96. Nat Immunol. 2000;1(2):151–5.CrossRefPubMed
30.
Xie Y, Bai O, Zhang H, Yuan J, Zong S, Chibbar R, et al. Membrane-bound HSP70-engineered myeloma cell-derived exosomes stimulate more efficient CD8(+) CTL- and NK-mediated antitumour immunity than exosomes released from heat-shocked tumour cells expressing cytoplasmic HSP70. J Cell Mol Med. 2010;14(11):2655–66.CrossRefPubMed
31.
Basu S, Srivastava PK. Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor- and peptide-specific immunity. J Exp Med. 1999;189(5):797–802.CrossRefPubMedCentralPubMed
32.
Robert J, Menoret A, Basu S, Cohen N, Srivastava PR. Phylogenetic conservation of the molecular and immunological properties of the chaperones gp96 and hsp70. Eur J Immunol. 2001;31(1):186–95.CrossRefPubMed
33.
Srivastava PK. Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens. Methods. 1997;12(2):165–71.CrossRefPubMed
34.
Lee HM, Choi EJ, Kim JH, Kim TD, Kim YK, Kang C, et al. A membranous form of ICAM-1 on exosomes efficiently blocks leukocyte adhesion to activated endothelial cells. Biochem Biophys Res Commun. 2010;397(2):251–6.CrossRefPubMed
35.
Nolte-'t Hoen EN, Buschow SI, Anderton SM, Stoorvogel W, Wauben MH. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood. 2009;113(9):1977–81.CrossRefPubMed
36.
Tanaka K, Kasahara M. The MHC class I ligand-generating system: roles of immunoproteasomes and the interferon-gamma-inducible proteasome activator PA28. Immunol Rev. 1998;163:161–76.CrossRefPubMed
37.
Fruh K, Yang Y. Antigen presentation by MHC class I and its regulation by interferon gamma. Curr Opin Immunol. 1999;11(1):76–81.CrossRefPubMed
38.
Dick TP, Ruppert T, Groettrup M, Kloetzel PM, Kuehn L, Koszinowski UH, et al. Coordinated dual cleavages induced by the proteasome regulator PA28 lead to dominant MHC ligands. Cell. 1996;86(2):253–62.CrossRefPubMed
39.
Kuehn L, Dahlmann B. Structural and functional properties of proteasome activator PA28. Mol Biol Rep. 1997;24(1–2):89–93.CrossRefPubMed
Metadata
Title
Proteomic analysis of exosomes derived from human lymphoma cells
Authors
Ye Yao
Wei Wei
Jing Sun
Linjun Chen
Xiaohui Deng
Liyuan Ma
Siguo Hao
Publication date
01-12-2015
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2015
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-014-0082-4

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