Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles

Laura M. Epple, Steve G. Griffiths, Anjelika M. Dechkovskaia, Nathaniel L. Dusto, Jason White, Rodney J. Ouellette, Thomas J. Anchordoquy, Lynne T. Bemis, Michael W. Graner

Research output: Contribution to journalArticle

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Abstract

Medulloblastomas are the most prevalent malignant pediatric brain tumors. Survival for these patients has remained largely the same for approximately 20 years, and our therapies for these cancers cause significant health, cognitive, behavioral and developmental sequelae for those who survive the tumor and their treatments. We obviously need a better understanding of the biology of these tumors, particularly with regard to their migratory/invasive behaviors, their proliferative propensity, and their abilities to deflect immune responses. Exosomes, virus-sized membrane vesicles released extracellularly from cells after formation in, and transit thru, the endosomal pathway, may play roles in medulloblastoma pathogenesis but are as yet unstudied in this disease. Here we characterized exosomes from a medulloblastoma cell line with biochemical and proteomic analyses, and included characterization of patient serum exosomes. Further scrutiny of the proteomic data suggested functional properties of the exosomes that are relevant to medulloblastoma tumor biology, including their roles as proliferation stimulants, their activities as attractants for tumor cell migration, and their immune modulatory impacts on lymphocytes. Aspects of this held true for exosomes from other medulloblastoma cell lines as well. Additionally, pathway analyses suggested a possible role for the transcription factor hepatocyte nuclear factor 4 alpha (HNF4A); however, inhibition of the protein's activity actually increased D283MED cell proliferation/clonogenecity, suggesting that HNF4A may act as a tumor suppressor in this cell line. Our work demonstrates that relevant functional properties of exosomes may be derived from appropriate proteomic analyses, which translate into mechanisms of tumor pathophysiology harbored in these extracellular vesicles.

Original languageEnglish (US)
Article numbere42064
JournalPloS one
Volume7
Issue number7
DOIs
StatePublished - Jul 27 2012

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exosomes
Exosomes
Medulloblastoma
Proteomics
proteomics
Tumors
neoplasms
Hepatocyte Nuclear Factor 4
Cells
Neoplasms
cell lines
hepatocytes
functional properties
Cell Line
suppressor cells
Biological Sciences
complications (disease)
attractants
Pediatrics
pathophysiology

Cite this

Epple, L. M., Griffiths, S. G., Dechkovskaia, A. M., Dusto, N. L., White, J., Ouellette, R. J., ... Graner, M. W. (2012). Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles. PloS one, 7(7), [e42064]. https://doi.org/10.1371/journal.pone.0042064

Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles. / Epple, Laura M.; Griffiths, Steve G.; Dechkovskaia, Anjelika M.; Dusto, Nathaniel L.; White, Jason; Ouellette, Rodney J.; Anchordoquy, Thomas J.; Bemis, Lynne T.; Graner, Michael W.

In: PloS one, Vol. 7, No. 7, e42064, 27.07.2012.

Research output: Contribution to journalArticle

Epple, LM, Griffiths, SG, Dechkovskaia, AM, Dusto, NL, White, J, Ouellette, RJ, Anchordoquy, TJ, Bemis, LT & Graner, MW 2012, 'Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles', PloS one, vol. 7, no. 7, e42064. https://doi.org/10.1371/journal.pone.0042064
Epple LM, Griffiths SG, Dechkovskaia AM, Dusto NL, White J, Ouellette RJ et al. Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles. PloS one. 2012 Jul 27;7(7). e42064. https://doi.org/10.1371/journal.pone.0042064
Epple, Laura M. ; Griffiths, Steve G. ; Dechkovskaia, Anjelika M. ; Dusto, Nathaniel L. ; White, Jason ; Ouellette, Rodney J. ; Anchordoquy, Thomas J. ; Bemis, Lynne T. ; Graner, Michael W. / Medulloblastoma exosome proteomics yield functional roles for extracellular vesicles. In: PloS one. 2012 ; Vol. 7, No. 7.
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