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Glioblastoma Microvesicles Transport RNA and Proteins, Promoting Tumor Growth

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Tumors of the Central Nervous System, Volume 11

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 11))

Abstract

The recent discovery that tumor-derived proteins and nucleic acid are carried in nano-sized vesicles in the plasma of patients with brain tumors has expanded opportunities for biomarker discovery and therapeutics. Through delivery of their contents to surrounding cells, these small extra-cellular vesicles secreted by tumors including glioblastomas are able to modulate their environment to promote tumor growth and survival. In this chapter, we discuss the potential use of small microvesicles as sources of tumor-specific biomarkers, mediators of therapy, and treatment monitoring. We review the normal physiology of these vesicles, their characterization, and new directions for research in this interesting field.

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References

  • Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624

    Article  PubMed  CAS  Google Scholar 

  • Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak J (2009) Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci U S A 106:3794–3799

    Article  PubMed Central  PubMed  Google Scholar 

  • Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ (2011) Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 29:341–345

    Article  PubMed  CAS  Google Scholar 

  • Arroyo JD, Chevillet JR, Kroh EM, Ruf IK, Pritchard CC, Gibson DF, Mitchell PS, Bennett CF, Pogosova-Agadjanyan EL, Stirewalt DL, Tait JF, Tewari M (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108:5003–5008

    Article  PubMed Central  PubMed  Google Scholar 

  • Balaj L, Lessard R, Dai L, Cho YJ, Pomeroy SL, Breakefield XO, Skog J (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bebawy M, Combes V, Lee E, Jaiswal R, Gong J, Bonhoure A, Grau GE (2009) Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells. Leukemia 23:1643–1649

    Article  PubMed  CAS  Google Scholar 

  • Castellana D, Zobairi F, Martinez MC, Panaro MA, Mitolo V, Freyssinet JM, Kunzelmann C (2009) Membrane microvesicles as actors in the establishment of a favorable prostatic tumoral niche: a role for activated fibroblasts and CX3CL1-CX3CR1 axis. Cancer Res 69:785–793

    Article  PubMed  CAS  Google Scholar 

  • Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, 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 (2010) Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 120:457–471

    PubMed Central  PubMed  CAS  Google Scholar 

  • Chen C, Skog J, Hsu CH, Lessard RT, Balaj L, Wurdinger T, Carter BS, Breakefield XO, Toner M, Irimia D (2010) Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip 10:505–511

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51

    Article  PubMed  CAS  Google Scholar 

  • Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    Article  PubMed  CAS  Google Scholar 

  • Fauré J, Lachenal G, Court M, Hirrlinger J, Chatellard-Causse C, Blot B, Grange J, Schoehn G, Goldberg Y, Boyer V, Kirchhoff F, Raposo G, Garin J, Sadoul R (2006) Exosomes are released by cultured cortical neurones. Mol Cell Neurosci 31:642–648

    Article  PubMed  CAS  Google Scholar 

  • Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD (2009) Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23:1541–1557

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hedlund M, Stenqvist AC, Nagaeva O, Kjellberg L, Wulff M, Baranov V, Mincheva-Nilsson L (2009) Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: evidence for immunosuppressive function. J Immunol 183:340–351

    Article  PubMed  CAS  Google Scholar 

  • Iero M, Valenti R, Huber V, Filipazzi P, Parmiani G, Fais S, Rivoltini L (2008) Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15:80–88

    Article  PubMed  CAS  Google Scholar 

  • Jeuken JW, Wesseling P (2010) MAPK pathway activation through BRAF gene fusion in pilocytic astrocytomas; a novel oncogenic fusion gene with diagnostic, prognostic, and therapeutic potential. J Pathol 222:324–328

    Article  PubMed  CAS  Google Scholar 

  • Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles exosomes. J Biol Chem 262:9412–9420

    PubMed  CAS  Google Scholar 

  • Koga K, Matsumoto K, Akiyoshi T, Kubo M, Yamanaka N, Tasaki A, Nakashima H, Nakamura M, Kuroki S, Tanaka M, Katano M (2005) Purification, characterization and biological significance of tumor-derived exosomes. Anticancer Res 25:3703–3707

    PubMed  CAS  Google Scholar 

  • Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, Marra M, Lugini L, Logozzi M, Lozupone F, Federici C, Iessi E, Parmiani G, Arancia G, Belardelli F, Fais S (2004) Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst 96:1702–1713

    Article  PubMed  CAS  Google Scholar 

  • Muralidharan-Chari V, Clancy JW, Sedgwick A, D’Souza-Schorey C (2010) Microvesicles: mediators of extracellular communication during cancer progression. J Cell Sci 123:1603–1611

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Noerholm M, Balaj L, Limperg T, Salehi A, Zhu LD, Hochberg FH, Breakefield XO, Carter BS, Skog J (2012) RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls. BMC Cancer 12:22

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Noushmehr H, Weisenberger DJ, Diefes K, Phillips HS, Pujara K, Berman BP, Pan F, Pelloski CE, Sulman EP, Bhat KP, Verhaak RG, Hoadley KA, Hayes DN, Perou CM, Schmidt HK, Ding L, Wilson RK, Van Den Berg D, Shen H, Bengtsson H, Neuvial P, Cope LM, Buckley J, Herman JG, Baylin SB, Laird PW, Aldape K, Network CGAR (2010) Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell 17:510–522

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Olver C, Vidal M (2007) Proteomic analysis of secreted exosomes. Subcell Biochem 43:99–131

    Article  PubMed  Google Scholar 

  • Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12:19–30; sup pp 11-13

    Article  PubMed  CAS  Google Scholar 

  • Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, de Gruijl TD, Würdinger T, Middeldorp JM (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A 107:6328–6333

    Article  PubMed Central  PubMed  Google Scholar 

  • Rabinowits G, Gerçel-Taylor C, Day JM, Taylor DD, Kloecker GH (2009) Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer 10:42–46

    Article  PubMed  CAS  Google Scholar 

  • Sabin KZ, Rovin RA, Lawrence JE, Belton RJ, Winn RJ (2012) 190 glioblastoma derived exosomes induce apoptosis in cytotoxic T cells through a Fas ligand mediated mechanism. Neurosurgery 71:E574

    Article  Google Scholar 

  • Safaei R, Larson BJ, Cheng TC, Gibson MA, Otani S, Naerdemann W, Howell SB (2005) Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells. Mol Cancer Ther 4:1595–1604

    Article  PubMed  CAS  Google Scholar 

  • Shedden K, Xie XT, Chandaroy P, Chang YT, Rosania GR (2003) Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles. Cancer Res 63:4331–4337

    PubMed  CAS  Google Scholar 

  • Skog J, Würdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, Curry WT, Carter BS, Krichevsky AM, Breakefield XO (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL (2010) Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells Treg. PLoS One 5:e11469

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Taylor DD, Doellgast GJ (1979) Quantitation of peroxidase-antibody binding to membrane fragments using column chromatography. Anal Biochem 98:53–59

    Article  PubMed  CAS  Google Scholar 

  • Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21

    Article  PubMed  CAS  Google Scholar 

  • Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007) Exosome- mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659

    Article  PubMed  CAS  Google Scholar 

  • van der Vos KE, Balaj L, Skog J, Breakefield XO (2011) Brain tumor microvesicles: insights into intercellular communication in the nervous system. Cell Mol Neurobiol 31:949–959

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. UCSD Neurosurgery, 3855 Health Science Drive #0987, San Diego, CA, 92093, USA

    David Gonda, Amit Goyal, Johnny Akers, Clark Chen & Bob Carter

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  1. David Gonda
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  2. Amit Goyal
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  3. Johnny Akers
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  4. Clark Chen
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  5. Bob Carter
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Corresponding author

Correspondence to Bob Carter .

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Editors and Affiliations

  1. Kean University, Room 213, Library building, Union, New Jersey, USA

    M.A. Hayat

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Gonda, D., Goyal, A., Akers, J., Chen, C., Carter, B. (2014). Glioblastoma Microvesicles Transport RNA and Proteins, Promoting Tumor Growth. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 11. Tumors of the Central Nervous System, vol 11. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7037-9_9

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  • DOI: https://doi.org/10.1007/978-94-007-7037-9_9

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