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Proteomic and immunologic analyses of brain tumor exosomes.

Publication ,  Journal Article
Graner, MW; Alzate, O; Dechkovskaia, AM; Keene, JD; Sampson, JH; Mitchell, DA; Bigner, DD
Published in: FASEB J
May 2009

Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30-100 nm membranous vesicles released from many cell types into the extracellular milieu; surprisingly, exosomes are virtually unstudied in neuro-oncology. These microvesicles were used as vaccines in other tumor settings, but their immunological significance is unevaluated in brain tumors. Our purpose here is to report the initial biochemical, proteomic, and immunological studies on murine brain tumor exosomes, following known procedures to isolate exosomes. Our findings show that these vesicles have biophysical characteristics and proteomic profiles similar to exosomes from other cell types but that brain tumor exosomes have unique features (e.g., very basic isoelectric points, expressing the mutated tumor antigen EGFRvIII and the putatively immunosuppressive cytokine TGF-beta). Administration of such exosomes into syngeneic animals produced both humoral and cellular immune responses in immunized hosts capable of rejecting subsequent tumor challenges but failed to prolong survival in established orthotopic models. Control animals received saline or cell lysate vaccines and showed no antitumor responses. Exosomes and microvesicles isolated from sera of patients with brain tumors also possess EGFR, EGFRvIII, and TGF-beta. We conclude that exosomes released from brain tumor cells are biochemically/biophysically like other exosomes and have immune-modulating properties. They can escape the blood-brain barrier, with potential systemic and distal signaling and immune consequences.

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Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

May 2009

Volume

23

Issue

5

Start / End Page

1541 / 1557

Location

United States

Related Subject Headings

  • Vaccination
  • Proteome
  • Mice
  • Humans
  • Glioma
  • Exosomes
  • Electrophoresis, Gel, Two-Dimensional
  • Cell Line, Tumor
  • Brain Neoplasms
  • Blotting, Western
 

Citation

APA
Chicago
ICMJE
MLA
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Graner, M. W., Alzate, O., Dechkovskaia, A. M., Keene, J. D., Sampson, J. H., Mitchell, D. A., & Bigner, D. D. (2009). Proteomic and immunologic analyses of brain tumor exosomes. FASEB J, 23(5), 1541–1557. https://doi.org/10.1096/fj.08-122184
Graner, Michael W., Oscar Alzate, Angelika M. Dechkovskaia, Jack D. Keene, John H. Sampson, Duane A. Mitchell, and Darell D. Bigner. “Proteomic and immunologic analyses of brain tumor exosomes.FASEB J 23, no. 5 (May 2009): 1541–57. https://doi.org/10.1096/fj.08-122184.
Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, et al. Proteomic and immunologic analyses of brain tumor exosomes. FASEB J. 2009 May;23(5):1541–57.
Graner, Michael W., et al. “Proteomic and immunologic analyses of brain tumor exosomes.FASEB J, vol. 23, no. 5, May 2009, pp. 1541–57. Pubmed, doi:10.1096/fj.08-122184.
Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD. Proteomic and immunologic analyses of brain tumor exosomes. FASEB J. 2009 May;23(5):1541–1557.

Published In

FASEB J

DOI

EISSN

1530-6860

Publication Date

May 2009

Volume

23

Issue

5

Start / End Page

1541 / 1557

Location

United States

Related Subject Headings

  • Vaccination
  • Proteome
  • Mice
  • Humans
  • Glioma
  • Exosomes
  • Electrophoresis, Gel, Two-Dimensional
  • Cell Line, Tumor
  • Brain Neoplasms
  • Blotting, Western