1932

Abstract

High-grade gliomas, particularly glioblastomas (grade IV), are devastating diseases with dismal prognoses; afflicted patients seldom live longer than 15 months, and their quality of life suffers immensely. Our current standard-of-care therapy has remained essentially unchanged for almost 15 years, with little new therapeutic progress. We desperately need a better biologic understanding of these complicated tumors in a complicated organ. One area of rejuvenated study relates to extracellular vesicles (EVs)—membrane-enclosed nano- or microsized particles that originate from the endosomal system or are shed from the plasma membrane. EVs contribute to tumor heterogeneity (including the maintenance of glioma stem cells or their differentiation), the impacts of hypoxia (angiogenesis and coagulopathies), interactions amid the tumor microenvironment (concerning the survival of astrocytes, neurons, endothelial cells, blood vessels, the blood–brain barrier, and the ensuing inflammation), and influences on the immune system (both stimulatory and suppressive). This article reviews glioma EVs and the ways that EVs manifest themselves as autocrine, paracrine, and endocrine factors in proximal and distal intra- and intercellular communications. The reader should note that there is much controversy, and indeed confusion, in the field over the exact roles for EVs in many biological processes, and we will engage some of these difficulties herein.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-083118-015324
2019-08-31
2024-12-05
Loading full text...

Full text loading...

/deliver/fulltext/genom/20/1/annurev-genom-083118-015324.html?itemId=/content/journals/10.1146/annurev-genom-083118-015324&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L et al. 2008. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 10:619–24
    [Google Scholar]
  2. 2.
    Altadill T, Campoy I, Lanau L, Gill K, Rigau M et al. 2016. Enabling metabolomics based biomarker discovery studies using molecular phenotyping of exosome-like vesicles. PLOS ONE 11:e0151339
    [Google Scholar]
  3. 3.
    Anand S, Samuel M, Kumar S, Mathivanan S 2019. Ticket to a bubble ride: cargo sorting into exosomes and extracellular vesicles. Biochim. Biophys. Acta Proteins Proteom. In press. https://doi.org/10.1016/j.bbapap.2019.02.005
    [Crossref] [Google Scholar]
  4. 4.
    Anderson HC. 1969. Vesicles associated with calcification in the matrix of epiphyseal cartilage. J. Cell Biol. 41:59–72
    [Google Scholar]
  5. 5.
    Andrews DW, Resnicoff M, Flanders AE, Kenyon L, Curtis M et al. 2001. Results of a pilot study involving the use of an antisense oligodeoxynucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J. Clin. Oncol. 19:2189–200
    [Google Scholar]
  6. 6.
    Balca-Silva J, Matias D, do Carmo A, Sarmento-Ribeiro AB, Lopes MC, Moura-Neto V 2019. Cellular and molecular mechanisms of glioblastoma malignancy: implications in resistance and therapeutic strategies. Semin. Cancer Biol. In press. https://doi.org/10.1016/j.semcancer.2018.09.007
    [Crossref] [Google Scholar]
  7. 7.
    Bastida E, Ordinas A, Escolar G, Jamieson GA 1984. Tissue factor in microvesicles shed from U87MG human glioblastoma cells induces coagulation, platelet aggregation, and thrombogenesis. Blood 64:177–84
    [Google Scholar]
  8. 8.
    Bennett IE, Guo H, Kountouri N, D'Abaco GM, Hovens CM et al. 2015. Preoperative biomarkers of tumour vascularity are elevated in patients with glioblastoma multiforme. J. Clin. Neurosci. 22:1802–8
    [Google Scholar]
  9. 9.
    Bloom HJ. 1982. Intracranial tumors: response and resistance to therapeutic endeavors, 1970–1980. Int. J. Radiat. Oncol. Biol. Phys. 8:1083–113
    [Google Scholar]
  10. 10.
    Bonucci E. 1967. Fine structure of early cartilage calcification. J. Ultrastruct. Res. 20:33–50
    [Google Scholar]
  11. 11.
    Boudot R, Miletic D, Dziuban P, Affolderbach C, Knapkiewicz P et al. 2011. First-order cancellation of the Cs clock frequency temperature-dependence in Ne-Ar buffer gas mixture. Opt. Express 19:3106–14
    [Google Scholar]
  12. 12.
    Bretting H, Konigsmann K. 1979. Investigations on the lectin-producing cells in the sponge Axinella polypoides (Schmidt). Cell Tissue Res 201:487–97
    [Google Scholar]
  13. 13.
    Bu N, Wu H, Sun B, Zhang G, Zhan S et al. 2011. Exosome-loaded dendritic cells elicit tumor-specific CD8+ cytotoxic T cells in patients with glioma. J. Neurooncol. 104:659–67
    [Google Scholar]
  14. 14.
    Bu N, Wu H, Zhang G, Ma X, Zhao P et al. 2015. Exosome from chaperone-rich cell lysates-loaded dendritic cells produced by CELLine 1000 culture system exhibits potent immune activity. Biochem. Biophys. Res. Commun. 456:513–18
    [Google Scholar]
  15. 15.
    Bu N, Wu H, Zhang G, Zhan S, Zhang R et al. 2015. Exosomes from dendritic cells loaded with chaperone-rich cell lysates elicit a potent T cell immune response against intracranial glioma in mice. J. Mol. Neurosci. 56:631–43
    [Google Scholar]
  16. 16.
    Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H 2012. The brain tumor microenvironment. Glia 60:502–14
    [Google Scholar]
  17. 17.
    Choi D, Montermini L, Kim DK, Meehan B, Roth FP, Rak J 2018. The impact of oncogenic EGFRvIII on the proteome of extracellular vesicles released from glioblastoma cells. Mol. Cell. Proteom. 17:1948–64
    [Google Scholar]
  18. 18.
    Cocucci E, Meldolesi J. 2015. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol 25:364–72
    [Google Scholar]
  19. 19.
    Couzin-Frankel J. 2013. Breakthrough of the year 2013. Cancer immunotherapy. Science 342:1432–33
    [Google Scholar]
  20. 20.
    D'Agostino S, Salamone M, Di Liegro I, Vittorelli ML 2006. Membrane vesicles shed by oligodendroglioma cells induce neuronal apoptosis. Int. J. Oncol. 29:1075–85
    [Google Scholar]
  21. 21.
    D'Asti E, Huang A, Kool M, Meehan B, Chan JA et al. 2016. Tissue factor regulation by miR-520g in primitive neuronal brain tumor cells: a possible link between oncomirs and the vascular tumor microenvironment. Am. J. Pathol. 186:446–59
    [Google Scholar]
  22. 22.
    De Robertis ED, Bennett HS 1955. Some features of the submicroscopic morphology of synapses in frog and earthworm. J. Biophys. Biochem. Cytol. 1:47–58
    [Google Scholar]
  23. 23.
    de Vrij J, Maas SL, Kwappenberg KM, Schnoor R, Kleijn A et al. 2015. Glioblastoma-derived extracellular vesicles modify the phenotype of monocytic cells. Int. J. Cancer 137:1630–42
    [Google Scholar]
  24. 24.
    Del Fattore A, Luciano R, Saracino R, Battafarano G, Rizzo C et al. 2015. Differential effects of extracellular vesicles secreted by mesenchymal stem cells from different sources on glioblastoma cells. Expert Opin. Biol. Ther. 15:495–504
    [Google Scholar]
  25. 25.
    Di Vizio D, Kim J, Hager MH, Morello M, Yang W et al. 2009. Oncosome formation in prostate cancer: association with a region of frequent chromosomal deletion in metastatic disease. Cancer Res 69:5601–9
    [Google Scholar]
  26. 26.
    Di Vizio D, Morello M, Dudley AC, Schow PW, Adam RM et al. 2012. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am. J. Pathol. 181:1573–84
    [Google Scholar]
  27. 27.
    Domenis R, Cesselli D, Toffoletto B, Bourkoula E, Caponnetto F et al. 2017. Systemic T cells immunosuppression of glioma stem cell-derived exosomes is mediated by monocytic myeloid-derived suppressor cells. PLOS ONE 12:e0169932
    [Google Scholar]
  28. 28.
    Dvorak HF. 2015. Tumors: wounds that do not heal—redux. Cancer Immunol. Res. 3:1–11
    [Google Scholar]
  29. 29.
    Epple LM, Griffiths SG, Dechkovskaia AM, Dusto NL, White J et al. 2012. Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles. PLOS ONE 7:e42064
    [Google Scholar]
  30. 30.
    Feng Q, Zhang C, Lum D, Druso JE, Blank B et al. 2017. A class of extracellular vesicles from breast cancer cells activates VEGF receptors and tumour angiogenesis. Nat. Commun. 8:14450
    [Google Scholar]
  31. 31.
    Fenstermaker RA, Ciesielski MJ, Qiu J, Yang N, Frank CL et al. 2016. Clinical study of a survivin long peptide vaccine (SurVaxM) in patients with recurrent malignant glioma. Cancer Immunol. Immunother. 65:1339–52
    [Google Scholar]
  32. 32.
    Figueroa J, Phillips LM, Shahar T, Hossain A, Gumin J et al. 2017. Exosomes from glioma-associated mesenchymal stem cells increase the tumorigenicity of glioma stem-like cells via transfer of miR-1587. Cancer Res 77:5808–19
    [Google Scholar]
  33. 33.
    Fox AS, Duggleby WF, Gelbart WM, Yoon SB 1970. DNA-induced transformation in Drosophila: evidence for transmission without integration. PNAS 67:1834–38
    [Google Scholar]
  34. 34.
    Fox AS, Yoon SB. 1970. DNA-induced transformation in Drosophila: locus-specificity and the establishment of transformed stocks. PNAS 67:1608–15
    [Google Scholar]
  35. 35.
    Fox AS, Yoon SB, Gelbart WM 1971. DNA-induced transformation in Drosophila: genetic analysis of transformed stocks. PNAS 68:342–46
    [Google Scholar]
  36. 36.
    Galbo PM Jr., Ciesielski MJ, Figel S, Maguire O, Qiu J et al. 2017. Circulating CD9+/GFAP+/survivin+ exosomes in malignant glioma patients following survivin vaccination. Oncotarget 8:114722–35
    [Google Scholar]
  37. 37.
    Godlewski J, Ferrer-Luna R, Rooj AK, Mineo M, Ricklefs F et al. 2017. MicroRNA signatures and molecular subtypes of glioblastoma: the role of extracellular transfer. Stem Cell Rep 8:1497–505
    [Google Scholar]
  38. 38.
    Goon PK, Boos CJ, Stonelake PS, Lip GY 2005. Circulating endothelial cells in malignant disease. Future Oncol 1:813–20
    [Google Scholar]
  39. 39.
    Gould SJ, Raposo G. 2013. As we wait: coping with an imperfect nomenclature for extracellular vesicles. J Extracell. Vesicles 2:20389
    [Google Scholar]
  40. 40.
    Graner MW. 2012. Brain tumor exosomes and microvesicles: pleiotropic effects from tiny cellular surrogates. Molecular Targets of CNS Tumors M Garami 43–78 London: InTechOpen
    [Google Scholar]
  41. 41.
    Graner MW. 2018. B cell exosomes/extracellular vesicles as vehicles of B cell antigen presentation: implications for cancer vaccine therapies. Diagnostic and Therapeutic Applications of Exosomes in Cancer MM Amiji, R Ramesh 325–64 London: Academic
    [Google Scholar]
  42. 42.
    Graner MW. 2018. Extracellular vesicles in cancer immune responses: roles of purinergic receptors. Semin. Immunopathol. 40:465–75
    [Google Scholar]
  43. 43.
    Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH et al. 2009. Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23:1541–57
    [Google Scholar]
  44. 44.
    Graner MW, Bigner DD. 2006. Therapeutic aspects of chaperones/heat-shock proteins in neuro-oncology. Expert Rev. Anticancer Ther. 6:679–95
    [Google Scholar]
  45. 45.
    Graner MW, Schnell S, Olin MR 2018. Tumor-derived exosomes, microRNAs, and cancer immune suppression. Semin. Immunopathol. 40:505–15
    [Google Scholar]
  46. 46.
    Graner MW, Zeng Y, Feng H, Katsanis E 2003. Tumor-derived chaperone-rich cell lysates are effective therapeutic vaccines against a variety of cancers. Cancer Immunol. Immunother. 52:226–34
    [Google Scholar]
  47. 47.
    Hallal S, Mallawaaratchy DM, Wei H, Ebrahimkhani S, Stringer BW et al. 2019. Extracellular vesicles released by glioblastoma cells stimulate normal astrocytes to acquire a tumor-supportive phenotype via p53 and MYC signaling pathways. Mol. Neurobiol. 56:4566–81
    [Google Scholar]
  48. 48.
    Hambardzumyan D, Gutmann DH, Kettenmann H 2016. The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci. 19:20–27
    [Google Scholar]
  49. 49.
    Han S, Feng S, Ren M, Ma E, Wang X et al. 2014. Glioma cell-derived placental growth factor induces regulatory B cells. Int. J. Biochem. Cell Biol. 57:63–68
    [Google Scholar]
  50. 50.
    Harding CV, Heuser JE, Stahl PD 1983. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 97:329–39
    [Google Scholar]
  51. 51.
    Harding CV, Heuser JE, Stahl PD 2013. Exosomes: looking back three decades and into the future. J. Cell Biol. 200:367–71
    [Google Scholar]
  52. 52.
    Hargadon KM, Johnson CE, Williams CJ 2018. Immune checkpoint blockade therapy for cancer: an overview of FDA-approved immune checkpoint inhibitors. Int. Immunopharmacol. 62:29–39
    [Google Scholar]
  53. 53.
    Hargett LA, Bauer NN. 2013. On the origin of microparticles: from “platelet dust” to mediators of intercellular communication. Pulm. Circ. 3:329–40
    [Google Scholar]
  54. 54.
    Harshyne LA, Hooper KM, Andrews EG, Nasca BJ, Kenyon LC et al. 2015. Glioblastoma exosomes and IGF-1R/AS-ODN are immunogenic stimuli in a translational research immunotherapy paradigm. Cancer Immunol. Immunother. 64:299–309
    [Google Scholar]
  55. 55.
    Harshyne LA, Nasca BJ, Kenyon LC, Andrews DW, Hooper DC 2016. Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients. Neuro-Oncology 18:206–15
    [Google Scholar]
  56. 56.
    Hellwinkel JE, Redzic JS, Harland TA, Gunaydin D, Anchordoquy TJ, Graner MW 2015. Glioma-derived extracellular vesicles selectively suppress immune responses. Neuro-Oncology 18:497–506
    [Google Scholar]
  57. 57.
    Hossain A, Gumin J, Gao F, Figueroa J, Shinojima N et al. 2015. Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway. Stem Cells 33:2400–15
    [Google Scholar]
  58. 58.
    Inda MM, Bonavia R, Mukasa A, Narita Y, Sah DW et al. 2010. Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev 24:1731–45
    [Google Scholar]
  59. 59.
    Iorgulescu JB, Ivan ME, Safaee M, Parsa AT 2016. The limited capacity of malignant glioma-derived exosomes to suppress peripheral immune effectors. J. Neuroimmunol. 290:103–8
    [Google Scholar]
  60. 60.
    Jeppesen DK, Hvam ML, Primdahl-Bengtson B, Boysen AT, Whitehead B et al. 2014. Comparative analysis of discrete exosome fractions obtained by differential centrifugation. J. Extracell. Vesicles 3:25011
    [Google Scholar]
  61. 61.
    Johnson E, Dickerson KL, Connolly ID, Hayden Gephart M 2018. Single-cell RNA-sequencing in glioma. Curr. Oncol. Rep. 20:42
    [Google Scholar]
  62. 62.
    Johnstone RM. 2005. Revisiting the road to the discovery of exosomes. Blood Cells Mol. Dis. 34:214–19
    [Google Scholar]
  63. 63.
    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. 262:9412–20
    [Google Scholar]
  64. 64.
    Jung CS, Foerch C, Schanzer A, Heck A, Plate KH et al. 2007. Serum GFAP is a diagnostic marker for glioblastoma multiforme. Brain 130:3336–41
    [Google Scholar]
  65. 65.
    Keerthikumar S, Gangoda L, Gho YS, Mathivanan S 2017. Bioinformatics tools for extracellular vesicles research. Methods Mol. Biol. 1545:189–96
    [Google Scholar]
  66. 66.
    Keklikoglou I, Cianciaruso C, Güç E, Squadrito ML, Spring LM et al. 2019. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat. Cell Biol. 21:190–202
    [Google Scholar]
  67. 67.
    Keshtkar S, Azarpira N, Ghahremani MH 2018. Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Res. Ther. 9:63
    [Google Scholar]
  68. 68.
    Kore RA, Abraham EC. 2014. Inflammatory cytokines, interleukin-1 beta and tumor necrosis factor-alpha, upregulated in glioblastoma multiforme, raise the levels of CRYAB in exosomes secreted by U373 glioma cells. Biochem. Biophys. Res. Commun. 453:326–31
    [Google Scholar]
  69. 69.
    Kore RA, Edmondson JL, Jenkins SV, Jamshidi-Parsian A, Dings RPM et al. 2018. Hypoxia-derived exosomes induce putative altered pathways in biosynthesis and ion regulatory channels in glioblastoma cells. Biochem. Biophys. Rep. 14:104–13
    [Google Scholar]
  70. 70.
    Kourembanas S. 2015. Exosomes: vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. Annu. Rev. Physiol. 77:13–27
    [Google Scholar]
  71. 71.
    Kowal J, Arras G, Colombo M, Jouve M, Morath JP et al. 2016. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. PNAS 113:E968–77
    [Google Scholar]
  72. 72.
    Kucharzewska P, Christianson HC, Welch JE, Svensson KJ, Fredlund E et al. 2013. Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. PNAS 110:7312–17
    [Google Scholar]
  73. 73.
    Kunigelis KE, Graner MW. 2015. The dichotomy of tumor exosomes (TEX) in cancer immunity: Is it all in the ConTEXt. ? Vaccines 3:1019–51
    [Google Scholar]
  74. 74.
    Kurywchak P, Tavormina J, Kalluri R 2018. The emerging roles of exosomes in the modulation of immune responses in cancer. Genome Med 10:23
    [Google Scholar]
  75. 75.
    Lang HL, Hu GW, Chen Y, Liu Y, Tu W et al. 2017. Glioma cells promote angiogenesis through the release of exosomes containing long non-coding RNA POU3F3. Eur. Rev. Med. Pharmacol. Sci. 21:959–72
    [Google Scholar]
  76. 76.
    Lang HL, Hu GW, Zhang B, Kuang W, Chen Y et al. 2017. Glioma cells enhance angiogenesis and inhibit endothelial cell apoptosis through the release of exosomes that contain long non-coding RNA CCAT2. Oncol. Rep. 38:785–98
    [Google Scholar]
  77. 77.
    Le DM, Besson A, Fogg DK, Choi KS, Waisman DM et al. 2003. Exploitation of astrocytes by glioma cells to facilitate invasiveness: a mechanism involving matrix metalloproteinase-2 and the urokinase-type plasminogen activator-plasmin cascade. J. Neurosci. 23:4034–43
    [Google Scholar]
  78. 78.
    Le Rhun E, Perry JR 2016. Vascular complications in glioma patients. Handb. Clin. Neurol. 134:251–66
    [Google Scholar]
  79. 79.
    Lee TH, D'Asti E, Magnus N, Al-Nedawi K, Meehan B, Rak J 2011. Microvesicles as mediators of intercellular communication in cancer—the emerging science of cellular ‘debris.’. Semin. Immunopathol. 33:455–67
    [Google Scholar]
  80. 80.
    Li CC, Eaton SA, Young PE, Lee M, Shuttleworth R et al. 2013. Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells. RNA Biol 10:1333–44
    [Google Scholar]
  81. 81.
    Liu H, Chen L, Liu J, Meng H, Zhang R et al. 2017. Co-delivery of tumor-derived exosomes with alpha-galactosylceramide on dendritic cell-based immunotherapy for glioblastoma. Cancer Lett 411:182–90
    [Google Scholar]
  82. 82.
    Liu S, Sun J, Lan Q 2014. Glioblastoma microvesicles promote endothelial cell proliferation through Akt/beta-catenin pathway. Int. J. Clin. Exp. Pathol. 7:4857–66
    [Google Scholar]
  83. 83.
    Liu ZM, Wang YB, Yuan XH 2013. Exosomes from murine-derived GL26 cells promote glioblastoma tumor growth by reducing number and function of CD8+ T cells. Asian Pac. J. Cancer Prev. 14:309–14
    [Google Scholar]
  84. 84.
    Lo Cicero A, Schiera G, Proia P, Saladino P, Savettieri G et al. 2011. Oligodendroglioma cells shed microvesicles which contain TRAIL as well as molecular chaperones and induce cell death in astrocytes. Int. J. Oncol. 39:1353–57
    [Google Scholar]
  85. 85.
    Lombardi G, Pambuku A, Bellu L, Farina M, Della Puppa A et al. 2017. Effectiveness of antiangiogenic drugs in glioblastoma patients: a systematic review and meta-analysis of randomized clinical trials. Crit. Rev. Oncol. Hematol. 111:94–102
    [Google Scholar]
  86. 86.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D et al. 2016. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803–20
    [Google Scholar]
  87. 87.
    Magana-Maldonado R, Chavez-Cortez EG, Olascoaga-Arellano NK, Lopez-Mejia M, Maldonado-Leal FM et al. 2016. Immunological evasion in glioblastoma. BioMed. Res. Int. 2016:7487313
    [Google Scholar]
  88. 88.
    Mahase S, Rattenni RN, Wesseling P, Leenders W, Baldotto C et al. 2017. Hypoxia-mediated mechanisms associated with antiangiogenic treatment resistance in glioblastomas. Am. J. Pathol. 187:940–53
    [Google Scholar]
  89. 89.
    Marleau AM, Chen CS, Joyce JA, Tullis RH 2012. Exosome removal as a therapeutic adjuvant in cancer. J. Transl. Med. 10:134
    [Google Scholar]
  90. 90.
    Mazzoleni S, Galli R. 2012. Gliomagenesis: a game played by few players or a team effort. ? Front. Biosci. (Elite Ed.) 4:205–13
    [Google Scholar]
  91. 91.
    McComb RD, Bigner DD. 1984. The biology of malignant gliomas—a comprehensive survey. Clin. Neuropathol. 3:93–106
    [Google Scholar]
  92. 92.
    Meehan B, Rak J, Di Vizio D 2016. Oncosomes – large and small: what are they, where they came from. ? J. Extracell. Vesicles 5:33109
    [Google Scholar]
  93. 93.
    Mildenberger I, Bunse L, Ochs K, Platten M 2017. The promises of immunotherapy in gliomas. Curr. Opin. Neurol. 30:650–58
    [Google Scholar]
  94. 94.
    Miller JJ, Wen PY. 2016. Emerging targeted therapies for glioma. Expert Opin. Emerg. Drugs 21:441–52
    [Google Scholar]
  95. 95.
    Minciacchi VR, Freeman MR, Di Vizio D 2015. Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes. Semin. Cell Dev. Biol. 40:41–51
    [Google Scholar]
  96. 96.
    Mirzaei R, Sarkar S, Dzikowski L, Rawji KS, Khan L et al. 2018. Brain tumor-initiating cells export tenascin-C associated with exosomes to suppress T cell activity. Oncoimmunology 7:e1478647
    [Google Scholar]
  97. 97.
    Mitchell P, Petfalski E, Shevchenko A, Mann M, Tollervey D 1997. The exosome: a conserved eukaryotic RNA processing complex containing multiple 3′→5′ exoribonucleases. Cell 91:457–66
    [Google Scholar]
  98. 98.
    Monteiro RQ, Lima LG, Gonçalves NP, Arruda de Souza MR, Leal AC et al. 2016. Hypoxia regulates the expression of tissue factor pathway signaling elements in a rat glioma model. Oncol. Lett. 12:315–22
    [Google Scholar]
  99. 99.
    Morello M, Minciacchi VR, de Candia P, Yang J, Posadas E et al. 2013. Large oncosomes mediate intercellular transfer of functional microRNA. Cell Cycle 12:3526–36
    [Google Scholar]
  100. 100.
    Muller L, Muller-Haegele S, Mitsuhashi M, Gooding W, Okada H, Whiteside TL 2015. Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival. Oncoimmunology 4:e1008347
    [Google Scholar]
  101. 101.
    Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G et al. 2011. Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with α-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J. Clin. Oncol. 29:330–36
    [Google Scholar]
  102. 102.
    Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y et al. 2017. CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro-Oncology 19:v1–88
    [Google Scholar]
  103. 103.
    Oushy S, Hellwinkel JE, Wang M, Nguyen GJ, Gunaydin D et al. 2018. Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype. Philos. Trans. R. Soc. Lond. B 373:20160477
    [Google Scholar]
  104. 104.
    Palomo L, Casal E, Royo F, Cabrera D, van-Liempd S, Falcon-Perez JM 2014. Considerations for applying metabolomics to the analysis of extracellular vesicles. Front. Immunol. 5:651
    [Google Scholar]
  105. 105.
    Pan BT, Johnstone RM. 1983. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33:967–78
    [Google Scholar]
  106. 106.
    Pavon LF, Sibov TT, de Souza AV, da Cruz EF, Malheiros SMF et al. 2018. Tropism of mesenchymal stem cell toward CD133+ stem cell of glioblastoma in vitro and promote tumor proliferation in vivo. Stem Cell Res. Ther. 9:310
    [Google Scholar]
  107. 107.
    Perng P, Lim M. 2015. Immunosuppressive mechanisms of malignant gliomas: parallels at non-CNS sites. Front. Oncol. 5:153
    [Google Scholar]
  108. 108.
    Pink RC, Elmusrati AA, Lambert D, Carter DRF 2018. Royal Society Scientific Meeting: extracellular vesicles in the tumour microenvironment. Philos. Trans. R. Soc. Lond. B 373:20170066
    [Google Scholar]
  109. 109.
    Podbielska M, Szulc ZM, Kurowska E, Hogan EL, Bielawski J et al. 2016. Cytokine-induced release of ceramide-enriched exosomes as a mediator of cell death signaling in an oligodendroglioma cell line. J. Lipid Res. 57:2028–39
    [Google Scholar]
  110. 110.
    Puhka M, Takatalo M, Nordberg ME, Valkonen S, Nandania J et al. 2017. Metabolomic profiling of extracellular vesicles and alternative normalization methods reveal enriched metabolites and strategies to study prostate cancer-related changes. Theranostics 7:3824–41
    [Google Scholar]
  111. 111.
    Qazi MA, Vora P, Venugopal C, Sidhu SS, Moffat J et al. 2017. Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann. Oncol. 28:1448–56
    [Google Scholar]
  112. 112.
    Ragusa M, Barbagallo C, Cirnigliaro M, Battaglia R, Brex D 2017. Asymmetric RNA distribution among cells and their secreted exosomes: biomedical meaning and considerations on diagnostic applications. Front. Mol. Biosci. 4:66
    [Google Scholar]
  113. 113.
    Reardon DA, Akabani G, Coleman RE, Friedman AH, Friedman HS et al. 2006. Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results. J. Clin. Oncol. 24:115–22
    [Google Scholar]
  114. 114.
    Redzic JS, Ung TH, Graner MW 2014. Glioblastoma extracellular vesicles: reservoirs of potential biomarkers. Pharmacogenom. Pers. Med. 7:65–77
    [Google Scholar]
  115. 115.
    Reynes G, Vila V, Fleitas T, Reganon E, Font de Mora J et al. 2013. Circulating endothelial cells and procoagulant microparticles in patients with glioblastoma: prognostic value. PLOS ONE 8:e69034
    [Google Scholar]
  116. 116.
    Rich JN, Guo C, McLendon RE, Bigner DD, Wang XF, Counter CM 2001. A genetically tractable model of human glioma formation. Cancer Res 61:3556–60
    [Google Scholar]
  117. 117.
    Ricklefs FL, Alayo Q, Krenzlin H, Mahmoud AB, Speranza MC et al. 2018. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci. Adv. 4:eaar2766
    [Google Scholar]
  118. 118.
    Ricklefs FL, Mineo M, Rooj AK, Nakano I, Charest A et al. 2016. Extracellular vesicles from high-grade glioma exchange diverse pro-oncogenic signals that maintain intratumoral heterogeneity. Cancer Res 76:2876–81
    [Google Scholar]
  119. 119.
    Rooj AK, Ricklefs F, Mineo M, Nakano I, Chiocca EA et al. 2017. MicroRNA-mediated dynamic bidirectional shift between the subclasses of glioblastoma stem-like cells. Cell Rep 19:2026–32
    [Google Scholar]
  120. 120.
    Santos PM, Butterfield LH. 2018. Dendritic cell-based cancer vaccines. J. Immunol. 200:443–49
    [Google Scholar]
  121. 121.
    Sartori MT, Della Puppa A, Ballin A, Campello E, Radu CM et al. 2013. Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: a potential prothrombotic role. Thromb. Haemost. 110:378–85
    [Google Scholar]
  122. 122.
    Sartori MT, Della Puppa A, Ballin A, Saggiorato G, Bernardi D et al. 2011. Prothrombotic state in glioblastoma multiforme: an evaluation of the procoagulant activity of circulating microparticles. J. Neurooncol. 104:225–31
    [Google Scholar]
  123. 123.
    Sharif S, Ghahremani MH, Soleimani M 2018. Delivery of exogenous miR-124 to glioblastoma multiform cells by Wharton's jelly mesenchymal stem cells decreases cell proliferation and migration, and confers chemosensitivity. Stem Cell Rev 14:236–46
    [Google Scholar]
  124. 124.
    Simon T, Pinioti S, Schellenberger P, Rajeeve V, Wendler F et al. 2018. Shedding of bevacizumab in tumour cells-derived extracellular vesicles as a new therapeutic escape mechanism in glioblastoma. Mol. Cancer 17:132
    [Google Scholar]
  125. 125.
    Simpson RJ, Mathivanan S. 2012. Extracellular microvesicles: the need for internationally recognised nomenclature and stringent purification criteria. J. Proteom. Bioinform. 5:ii
    [Google Scholar]
  126. 126.
    Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L et al. 2008. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 10:1470–76
    [Google Scholar]
  127. 127.
    Skotland T, Sandvig K, Llorente A 2017. Lipids in exosomes: current knowledge and the way forward. Prog. Lipid Res. 66:30–41
    [Google Scholar]
  128. 128.
    Smyth T, Kullberg M, Malik N, Smith-Jones P, Graner MW, Anchordoquy TJ 2015. Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J. Control. Release 199:145–55
    [Google Scholar]
  129. 129.
    Spinelli C, Montermini L, Meehan B, Brisson AR, Tan S et al. 2018. Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell-stimulating activities. J. Extracell. Vesicles 7:1490144
    [Google Scholar]
  130. 130.
    Stegmayr B, Ronquist G. 1982. Promotive effect on human sperm progressive motility by prostasomes. Urol. Res. 10:253–57
    [Google Scholar]
  131. 131.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B et al. 2005. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352:987–96
    [Google Scholar]
  132. 132.
    Sullivan BA, Kronenberg M. 2005. Activation or anergy: NKT cells are stunned by α-galactosylceramide. J. Clin. Investig. 115:2328–29
    [Google Scholar]
  133. 133.
    Sun X, Ma X, Wang J, Zhao Y, Wang Y et al. 2017. Glioma stem cells-derived exosomes promote the angiogenic ability of endothelial cells through miR-21/VEGF signal. Oncotarget 8:36137–48
    [Google Scholar]
  134. 134.
    Sundarraj N, Schachner M, Pfeiffer SE 1975. Biochemically differentiated mouse glial lines carrying a nervous system specific cell surface antigen (NS-1). PNAS 72:1927–31
    [Google Scholar]
  135. 135.
    Svensson KJ, Kucharzewska P, Christianson HC, Skold S, Lofstedt T et al. 2011. Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells. PNAS 108:13147–52
    [Google Scholar]
  136. 136.
    Taheri B, Soleimani M, Aval SF, Memari F, Zarghami N 2018. C6 glioma-derived microvesicles stimulate the proliferative and metastatic gene expression of normal astrocytes. Neurosci. Lett. 685:173–78
    [Google Scholar]
  137. 137.
    Thaler J, Ay C, Mackman N, Bertina RM, Kaider A et al. 2012. Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients. J. Thromb. Haemost. 10:1363–70
    [Google Scholar]
  138. 138.
    Thompson EM, Frenkel EP, Neuwelt EA 2011. The paradoxical effect of bevacizumab in the therapy of malignant gliomas. Neurology 76:87–93
    [Google Scholar]
  139. 139.
    Todorova D, Simoncini S, Lacroix R, Sabatier F, Dignat-George F 2017. Extracellular vesicles in angiogenesis. Circ. Res. 120:1658–73
    [Google Scholar]
  140. 140.
    Trams EG, Lauter CJ, Salem N Jr., Heine U 1981. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim. Biophys. Acta 645:63–70
    [Google Scholar]
  141. 141.
    Treps L, Edmond S, Harford-Wright E, Galan-Moya EM, Schmitt A et al. 2016. Extracellular vesicle-transported Semaphorin3A promotes vascular permeability in glioblastoma. Oncogene 35:2615–23
    [Google Scholar]
  142. 142.
    Treps L, Perret R, Edmond S, Ricard D, Gavard J 2017. Glioblastoma stem-like cells secrete the pro-angiogenic VEGF-A factor in extracellular vesicles. J. Extracell. Vesicles 6:1359479
    [Google Scholar]
  143. 143.
    Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9:654–59
    [Google Scholar]
  144. 144.
    van der Pol E, Boing AN, Gool EL, Nieuwland R 2016. Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles. J. Thromb. Haemost. 14:48–56
    [Google Scholar]
  145. 145.
    van der Vos KE, Abels ER, Zhang X, Lai C, Carrizosa E et al. 2016. Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain. Neuro-Oncology 18:58–69
    [Google Scholar]
  146. 146.
    van Es N, Bleker S, Sturk A, Nieuwland R 2015. Clinical significance of tissue factor-exposing microparticles in arterial and venous thrombosis. Semin. Thromb. Hemost. 41:718–27
    [Google Scholar]
  147. 147.
    Vega EA, Graner MW, Sampson JH 2008. Combating immunosuppression in glioma. Future Oncol 4:433–42
    [Google Scholar]
  148. 148.
    Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y et al. 2010. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110
    [Google Scholar]
  149. 149.
    Waldowska M, Bojarska-Junak A, Rolinski J 2017. A brief review of clinical trials involving manipulation of invariant NKT cells as a promising approach in future cancer therapies. Cent. Eur. J. Immunol. 42:181–95
    [Google Scholar]
  150. 150.
    Wang K, Ye L, Lu H, Chen H, Zhang Y et al. 2017. TNF-α promotes extracellular vesicle release in mouse astrocytes through glutaminase. J. Neuroinflamm. 14:87
    [Google Scholar]
  151. 151.
    Wei JW, Cai JQ, Fang C, Tan YL, Huang K et al. 2017. Signal peptide peptidase, encoded by HM13, contributes to tumor progression by affecting EGFRvIII secretion profiles in glioblastoma. CNS Neurosci. Ther. 23:257–65
    [Google Scholar]
  152. 152.
    Weller M, Roth P, Preusser M, Wick W, Reardon DA et al. 2017. Vaccine-based immunotherapeutic approaches to gliomas and beyond. Nat. Rev. Neurol. 13:363–74
    [Google Scholar]
  153. 153.
    Willms E, Johansson HJ, Mager I, Lee Y, Blomberg KE et al. 2016. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci. Rep. 6:22519
    [Google Scholar]
  154. 154.
    Witwer KW, Soekmadji C, Hill AF, Wauben MH, Buzas EI et al. 2017. Updating the MISEV minimal requirements for extracellular vesicle studies: building bridges to reproducibility. J. Extracell. Vesicles 6:1396823
    [Google Scholar]
  155. 155.
    Wolf P. 1967. The nature and significance of platelet products in human plasma. Br. J. Haematol. 13:269–88
    [Google Scholar]
  156. 156.
    Wong ML, Prawira A, Kaye AH, Hovens CM 2009. Tumour angiogenesis: its mechanism and therapeutic implications in malignant gliomas. J. Clin. Neurosci. 16:1119–30
    [Google Scholar]
  157. 157.
    Wurdinger T, Deumelandt K, van der Vliet HJ, Wesseling P, de Gruijl TD 2014. Mechanisms of intimate and long-distance cross-talk between glioma and myeloid cells: how to break a vicious cycle. Biochim. Biophys. Acta 1846:560–75
    [Google Scholar]
  158. 158.
    Xu R, Greening DW, Rai A, Ji H, Simpson RJ 2015. Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct. Methods 87:11–25
    [Google Scholar]
  159. 159.
    Yan K, Yang K, Rich JN 2013. The evolving landscape of glioblastoma stem cells. Curr. Opin. Neurol. 26:701–7
    [Google Scholar]
  160. 160.
    Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE et al. 2015. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 4:27066
    [Google Scholar]
  161. 161.
    Yang Y, Boza-Serrano A, Dunning CJR, Clausen BH, Lambertsen KL, Deierborg T 2018. Inflammation leads to distinct populations of extracellular vesicles from microglia. J. Neuroinflamm. 15:168
    [Google Scholar]
  162. 162.
    Zabeo D, Cvjetkovic A, Lasser C, Schorb M, Lotvall J, Hoog JL 2017. Exosomes purified from a single cell type have diverse morphology. J. Extracell. Vesicles 6:1329476
    [Google Scholar]
  163. 163.
    Zhang G, Zhang Y, Cheng S, Wu Z, Liu F, Zhang J 2017. CD133 positive U87 glioblastoma cells-derived exosomal microRNAs in hypoxia- versus normoxia-microenviroment. J. Neurooncol. 135:37–46
    [Google Scholar]
  164. 164.
    Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z et al. 2018. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat. Cell Biol. 20:332–43
    [Google Scholar]
  165. 165.
    Zhang J, Williams BM, Lawman S, Atkinson D, Zhang Z et al. 2017. Non-destructive analysis of flake properties in automotive paints with full-field optical coherence tomography and 3D segmentation. Opt. Express 25:18614–28
    [Google Scholar]
  166. 166.
    Zhao C, Wang H, Xiong C, Liu Y 2018. Hypoxic glioblastoma release exosomal VEGF-A induce the permeability of blood-brain barrier. Biochem. Biophys. Res. Commun. 502:324–31
    [Google Scholar]
/content/journals/10.1146/annurev-genom-083118-015324
Loading
/content/journals/10.1146/annurev-genom-083118-015324
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error