Skip to main content

Advertisement

SpringerLink
Log in

Exosomes as Tools to Suppress Primary Brain Tumor

  • Review Paper
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Exosomes are small microvesicles released by cells that efficiently transfer their molecular cargo to other cells, including tumor. Exosomes may pass the blood–brain barrier and have been demonstrated to deliver RNAs contained within to brain. As they are non-viable, the risk profile of exosomes is thought to be less than that of cellular therapies. Exosomes can be manufactured at scale in culture, and exosomes can be engineered to incorporate therapeutic miRNAs, siRNAs, or chemotherapeutic molecules. As natural biological delivery vehicles, interest in the use of exosomes as therapeutic delivery agents is growing. We previously demonstrated a novel treatment whereby mesenchymal stromal cells were employed to package tumor-suppressing miR-146b into exosomes, which were then used to reduce malignant glioma growth in rat. The use of exosomes to raise the immune system against tumor is also drawing interest. Exosomes from dendritic cells which are antigen-presenting, and have been used for treatment of brain tumor may be divided into three categories: (1) exosomes for immunomodulation-based therapy, (2) exosomes as delivery vehicles for anti-tumor nucleotides, and (3) exosomes as drug delivery vehicles. Here, we will provide an overview of these three applications of exosomes to treat brain tumor, and examine their prospects on the long road to clinical use.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • 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  CAS  PubMed  Google Scholar 

  • Andre F et al (2002) Tumor-derived exosomes: a new source of tumor rejection antigens. Vaccine 20(Suppl 4):A28–A31

    Article  CAS  PubMed  Google Scholar 

  • Anthony DF, Shiels PG (2013) Exploiting paracrine mechanisms of tissue regeneration to repair damaged organs. Transpl Res 2:10. doi:10.1186/2047-1440-2-10

    Article  CAS  Google Scholar 

  • Ardon H et al (2012) Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol Immunother 61:2033–2044

    Article  CAS  PubMed  Google Scholar 

  • Arroyo JD et al (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA 108:5003–5008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arslantas A et al (2007) Genomic alterations in low-grade, anaplastic astrocytomas and glioblastomas. Pathol Oncol Res 13:39–46

    Article  CAS  PubMed  Google Scholar 

  • Azmi AS, Bao B, Sarkar FH (2013) Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev 32:623–642

    Article  CAS  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  PubMed Central  CAS  Google Scholar 

  • Bao S et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760

    Article  CAS  PubMed  Google Scholar 

  • Barbano R et al (2014) A miRNA signature for defining aggressive phenotype and prognosis in gliomas. PLoS One 9:e108950

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barua NU, Gill SS, Love S (2014) Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations. Brain Pathol 24(2):117–127

    Article  CAS  PubMed  Google Scholar 

  • Baxevanis CN, Papamichail M, Perez SA (2015) Prostate cancer vaccines: the long road to clinical application. Cancer Immunol Immunother 64:401–408

    Article  CAS  PubMed  Google Scholar 

  • Bronisz A et al (2014) Extracellular vesicles modulate the glioblastoma microenvironment via a tumor suppression signaling network directed by miR-1. Cancer Res 74:738–750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bu N et al (2015a) Exosome from chaperone-rich cell lysates-loaded dendritic cells produced by CELLine 1000 culture system exhibits potent immune activity. Biochem Biophys Res Commun 456:513–518

    Article  CAS  PubMed  Google Scholar 

  • Bu N et al (2015b) 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 56:631–643

    Article  CAS  PubMed  Google Scholar 

  • Challagundla KB et al (2015) Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy. J Natl Cancer Inst. doi:10.1093/jnci/djv135

    PubMed  Google Scholar 

  • Chaput N, Taieb J, Schartz NE, Andre F, Angevin E, Zitvogel L (2004) Exosome-based immunotherapy Cancer Immunol Immunother 53:234–239

    Article  CAS  PubMed  Google Scholar 

  • Chen KG et al (2006) Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas. Proc Natl Acad Sci USA 103:9903–9907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen TS et al (2011) Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs. J Transl Med 9:47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho DY et al (2013) Targeting cancer stem cells for treatment of glioblastoma multiforme. Cell Transplant 22:731–739

    Article  PubMed  Google Scholar 

  • Christianson HC, Svensson KJ, van Kuppevelt TH, Li JP, Belting M (2013) Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci USA 110:17380–17385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cocucci E, Meldolesi J (2015) Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol 25:364–372

    Article  CAS  PubMed  Google Scholar 

  • Delcayre A, Shu H, Le Pecq JB (2005) Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature’s antigen delivery pathway. Expert Rev Anticancer Ther 5:537–547

    Article  CAS  PubMed  Google Scholar 

  • Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 113(19):3365–3374

    CAS  PubMed  Google Scholar 

  • Dillman RO et al (2004) Intracavitary placement of autologous lymphokine-activated killer (LAK) cells after resection of recurrent glioblastoma. J Immunother 27:398–404

    Article  PubMed  Google Scholar 

  • El-Andaloussi S et al (2012) Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc 7:2112–2126

    Article  CAS  PubMed  Google Scholar 

  • Escudier B et al (2005) Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial. J Transl Med 3:10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fabbri M, Croce CM, Calin GA (2008) MicroRNAs Cancer J 14:1–6

    Article  CAS  PubMed  Google Scholar 

  • Feng D et al (2010) Cellular internalization of exosomes occurs through phagocytosis. Traffic 11:675–687

    Article  CAS  PubMed  Google Scholar 

  • Gabriely G et al (2011) Human glioma growth is controlled by microRNA-10b. Cancer Res 71:3563–3572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallo A, Tandon M, Alevizos I, Illei GG (2012) The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS ONE 7:e30679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Geletneky K et al (2012) Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol. BMC Cancer 12:99

    Article  PubMed  PubMed Central  Google Scholar 

  • Gheldof D, Mullier F, Chatelain B, Dogne JM, Chatelain C (2013) Inhibition of tissue factor pathway inhibitor increases the sensitivity of thrombin generation assay to procoagulant microvesicles. Blood Coagul Fibrinolysis 24:567–572. doi:10.1097/MBC.0b013e328360a56e

    Article  CAS  PubMed  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  CAS  PubMed  PubMed Central  Google Scholar 

  • Guduric-Fuchs J, O’Connor A, Camp B, O’Neill CL, Medina RJ, Simpson DA (2012) Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genom 13:357

    Article  CAS  Google Scholar 

  • Hagiwara K, Ochiya T, Kosaka N (2014) A paradigm shift for extracellular vesicles as small RNA carriers: from cellular waste elimination to therapeutic applications. Drug Deliv Transl Res 4:31–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heddleston JM et al (2011) Glioma stem cell maintenance: the role of the microenvironment. Curr Pharm Des 17:2386–2401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu G, Drescher KM, Chen XM (2012) Exosomal miRNAs: Biological Properties and Therapeutic Potential. Front Genet 3:56

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iorio MV, Croce CM (2012a) MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med 4:143–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iorio MV, Croce CM (2012b) microRNA involvement in human cancer. Carcinogenesis 33:1126–1133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M (2014) A comprehensive overview of exosomes as drug delivery vehicles—endogenous nanocarriers for targeted cancer therapy. Biochim Biophys Acta 1846:75–87

    CAS  PubMed  Google Scholar 

  • Kahlert C, Kalluri R (2011) Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berl) 91:431–437

    Article  CAS  Google Scholar 

  • Kang TW et al (2014) Growth arrest and forced differentiation of human primary glioblastoma multiforme by a novel small molecule. Sci Rep 4:5546

    CAS  PubMed  PubMed Central  Google Scholar 

  • Katakowski M, Buller B, Wang X, Rogers T, Chopp M (2010a) Functional microRNA is transferred between glioma cells. Cancer Res 70:8259–8263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katakowski M, Zheng X, Jiang F, Rogers T, Szalad A, Chopp M (2010b) MiR-146b-5p suppresses EGFR expression and reduces in vitro migration and invasion of glioma. Cancer Invest 28:1024–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katakowski M et al (2012) Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett 335:201–204

    Article  CAS  Google Scholar 

  • Keller S, Ridinger J, Rupp AK, Janssen JW, Altevogt P (2011) Body fluid derived exosomes as a novel template for clinical diagnostics. J Transl Med 9:86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kooijmans SA, Vader P, van Dommelen SM, van Solinge WW, Schiffelers RM (2012) Exosome mimetics: a novel class of drug delivery systems. Int J Nanomed 7:1525–1541. doi:10.2147/IJN.S29661

    CAS  Google Scholar 

  • Kooijmans SA et al (2013) Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles. J Control Release 172:229–238

    Article  CAS  PubMed  Google Scholar 

  • Lai RC, Yeo RW, Tan KH, Lim SK (2013) Exosomes for drug delivery—a novel application for the mesenchymal stem cell. Biotechnol Adv 31:543–551

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, El Andaloussi S, Wood MJ (2012) Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet 21:R125–R134

    Article  CAS  PubMed  Google Scholar 

  • Li J, Sherman-Baust CA, Tsai-Turton M, Bristow RE, Roden RB, Morin PJ (2009) Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer. BMC Cancer 9:244

    Article  PubMed  PubMed Central  Google Scholar 

  • Markert JM et al (2009) Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Mol Ther 17:199–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marsh M, van Meer G (2008) Cell biology. No ESCRTs for exosomes. Science 319:1191–1192

    Article  CAS  PubMed  Google Scholar 

  • Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920

    Article  CAS  PubMed  Google Scholar 

  • Meckes DG Jr et al (2013) Modulation of B-cell exosome proteins by gamma herpesvirus infection. Proc Natl Acad Sci USA. doi:10.1073/pnas.1303906110

    PubMed  PubMed Central  Google Scholar 

  • Miller IV, Grunewald TG (2015) Tumour-derived exosomes: tiny envelopes for big stories. Biol Cell. doi:10.1111/boc.201400095

    PubMed  Google Scholar 

  • Mittelbrunn M, Sanchez-Madrid F (2012) Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol 13:328–335

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mittelbrunn M et al (2012) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2:282

    Article  CAS  Google Scholar 

  • Momen-Heravi F, Bala S, Bukong T, Szabo G (2014) Exosome-mediated delivery of functionally active miRNA-155 inhibitor to macrophages. Nanomedicine 10(7):1517–1527

    CAS  PubMed  PubMed Central  Google Scholar 

  • Morse MA et al (2005) A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med 3:9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Munoz JL, Bliss SA, Greco SJ, Ramkissoon SH, Ligon KL, Rameshwar P (2013) Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Mol Ther Nucleic Acids 2:e126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nazarenko I, Rupp AK, Altevogt P (2013) Exosomes as a potential tool for a specific delivery of functional molecules. Methods Mol Biol 1049:495–511

    Article  CAS  PubMed  Google Scholar 

  • Nicoloso MS, Calin GA (2008) MicroRNA involvement in brain tumors: from bench to bedside. Brain Pathol 18:122–129

    Article  CAS  PubMed  Google Scholar 

  • Nolte-’t Hoen EN, Buermans HP, Waasdorp M, Stoorvogel W, Wauben MH, t Hoen PA (2012) Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res 40:9272–9285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ohno S et al (2013) Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther 21:185–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okada H et al (2011) Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol 29:330–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ono M et al (2014) Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal 7:ra63

    Article  PubMed  CAS  Google Scholar 

  • Oshiro S et al (2006) Evaluation of intratumoral administration of tumor necrosis factor-alpha in patients with malignant glioma. Anticancer Res 26:4027–4032

    CAS  PubMed  Google Scholar 

  • Papagiannakopoulos T, Shapiro A, Kosik KS (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 68:8164–8172

    Article  CAS  PubMed  Google Scholar 

  • Penfornis P, Vallabhaneni KC, Whitt J, Pochampally R (2015) Extracellular vesicles as carriers of microRNA, proteins and lipids in tumor microenvironment. Int J Cancer. doi:10.1002/ijc.29417

    PubMed  Google Scholar 

  • Pershouse MA, Stubblefield E, Hadi A, Killary AM, Yung WK, Steck PA (1993) Analysis of the functional role of chromosome 10 loss in human glioblastomas. Cancer Res 53:5043–5050

    CAS  PubMed  Google Scholar 

  • Piwecka M et al (2015) Comprehensive analysis of microRNA expression profile in malignant glioma tissues. Mol Oncol 9:1324–1340

    Article  CAS  PubMed  Google Scholar 

  • Pritchard AL et al (2015) Exome sequencing to predict neoantigens in melanoma. Cancer Immunol Res. doi:10.1158/2326-6066

    PubMed  Google Scholar 

  • Qin J, Xu Q (2014) Functions and application of exosomes. Acta Pol Pharm 71:537–543

    PubMed  Google Scholar 

  • Ramachandran S, Palanisamy V (2012) Horizontal transfer of RNAs: exosomes as mediators of intercellular communication. Wiley Interdiscip Rev RNA 3:286–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rana S, Yue S, Stadel D, Zoller M (2012) Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int J Biochem Cell Biol 44:1574–1584

    Article  CAS  PubMed  Google Scholar 

  • Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172

    Article  CAS  PubMed  Google Scholar 

  • Rasheed BK, Fuller GN, Friedman AH, Bigner DD, Bigner SH (1992) Loss of heterozygosity for 10q loci in human gliomas. Genes Chromosomes Cancer 5:75–82

    Article  CAS  PubMed  Google Scholar 

  • Romagnoli GG, Zelante BB, Toniolo PA, Migliori IK, Barbuto JA (2015) Dendritic cell-derived exosomes may be a tool for cancer immunotherapy by converting tumor cells into immunogenic targets. Front Immunol 5:692

    Article  PubMed  PubMed Central  CAS  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  CAS  PubMed  Google Scholar 

  • Saito R et al (2006) Tissue affinity of the infusate affects the distribution volume during convection-enhanced delivery into rodent brains: implications for local drug delivery. J Neurosci Methods 154:225–232

    Article  CAS  PubMed  Google Scholar 

  • Salmaggi A et al (2006) Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype. Glia 54:850–860

    Article  PubMed  Google Scholar 

  • Sampson JH et al (2009) An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme. Mol Cancer Ther 8:2773–2779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santiago-Dieppa DR, Steinberg J, Gonda D, Cheung VJ, Carter BS, Chen CC (2014) Extracellular vesicles as a platform for ‘liquid biopsy’ in glioblastoma patients. Expert Rev Mol Diagn 14:819–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shao H et al (2012) Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy. Nat Med 18:1835–1840

    Article  CAS  PubMed  PubMed Central  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

    CAS  PubMed  Google Scholar 

  • Shelke GV, Lasser C, Gho YS, Lotvall J (2014) Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum. J Extracell Vesicles. doi:10.3402/jev.v3.24783

    PubMed  PubMed Central  Google Scholar 

  • Shimbo K, Miyaki S, Ishitobi H, Kato Y, Kubo T, Shimose S, Ochi M (2014) Exosome-formed synthetic microRNA-143 is transferred to osteosarcoma cells and inhibits their migration. Biochem Biophys Res Commun 445:381–387

    Article  CAS  PubMed  Google Scholar 

  • Silber J, James CD, Hodgson JG (2009) microRNAs in gliomas: small regulators of a big problem. Neuromolecular Med 11:208–222

    Article  CAS  PubMed  Google Scholar 

  • Singh M, Overwijk WW (2015) Intratumoral immunotherapy for melanoma Cancer. Immunol Immunother 64:911–921

    Article  CAS  Google Scholar 

  • Skog J et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 199:145–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun Y, Liu J (2014) Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances. Clin Ther 36(6):863–872

    Article  PubMed  Google Scholar 

  • Sun D et al (2010) A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther 18:1606–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan CY, Lai RC, Wong W, Dan YY, Lim SK, Ho HK (2014) Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther 5:76

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tavoosidana G et al (2011) Multiple recognition assay reveals prostasomes as promising plasma biomarkers for prostate cancer. Proc Natl Acad Sci USA 108:8809–8814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thery C (2011) Exosomes: secreted vesicles and intercellular communications F1000. Biol Rep 3:15

    Google Scholar 

  • Tian Y et al (2014) A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 35:2383–2390

    Article  CAS  PubMed  Google Scholar 

  • Tickner JA, Urquhart AJ, Stephenson SA, Richard DJ, O’Byrne KJ (2014) Functions and therapeutic roles of exosomes in cancer Front. Oncol 4:127

    Google Scholar 

  • Turner JD, Williamson R, Almefty KK, Nakaji P, Porter R, Tse V, Kalani MY (2010) The many roles of microRNAs in brain tumor biology. Neurosurg Focus 28:E3

    Article  PubMed  Google Scholar 

  • Utsugi-Kobukai S, Fujimaki H, Hotta C, Nakazawa M, Minami M (2003) MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells. Immunol Lett 89:125–131

    Article  CAS  PubMed  Google Scholar 

  • 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 9:654–659

    Article  CAS  PubMed  Google Scholar 

  • Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vik-Mo EO et al (2013) Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma. Cancer Immunol Immunother 62:1499–1509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Villarroya-Beltri C et al (2013) Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 4:2980

    Article  CAS  Google Scholar 

  • Wahlgren J, De LKT, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, Valadi H (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 40:e130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wheeler CJ et al (2008) Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients. Cancer Res 68:5955–5964

    Article  CAS  PubMed  Google Scholar 

  • Wolfers J et al (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7:297–303

    Article  CAS  PubMed  Google Scholar 

  • Xin H et al (2012) Exosome mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 30(7):1556–1564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xin H, Li Y, Chopp M (2014) Exosomes/miRNAs as mediating cell-based therapy of stroke Front Cell Neurosci 8:377

    PubMed  Google Scholar 

  • Yang C, Robbins PD (2011) The roles of tumor-derived exosomes in cancer pathogenesis. Clin Dev Immunol 2011:842849

    PubMed  PubMed Central  Google Scholar 

  • Yang T et al (2015) Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res 32:2003–2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeo RW, Lai RC, Zhang B, Tan SS, Yin Y, Teh BJ, Lim SK (2013) Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery. Adv Drug Deliv Rev 65:336–341

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Dutta A, Abounader R (2012) The role of microRNAs in glioma initiation and progression. Front Biosci 17:700–712

    Article  CAS  Google Scholar 

  • Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A, Xiong Y (2015) Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. J Neurosurg 122:856–867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou J et al (2013) Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma. Proc Natl Acad Sci USA 110:11751–11756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zitvogel L et al (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4:594–600

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Henry Ford Hospital, Detroit, MI, USA

    Mark Katakowski & Michael Chopp

  2. Department of Physics, Oakland University, Rochester, MI, USA

    Michael Chopp

Authors
  1. Mark Katakowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Chopp
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Chopp.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Katakowski, M., Chopp, M. Exosomes as Tools to Suppress Primary Brain Tumor. Cell Mol Neurobiol 36, 343–352 (2016). https://doi.org/10.1007/s10571-015-0280-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-015-0280-9

Keywords

Search

Navigation