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Open Access 01-01-2017 | Laboratory Investigation

Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease

Authors: Duthika M. Mallawaaratchy, Susannah Hallal, Ben Russell, Linda Ly, Saeideh Ebrahimkhani, Heng Wei, Richard I. Christopherson, Michael E. Buckland, Kimberley L. Kaufman

Published in: Journal of Neuro-Oncology | Issue 2/2017

Abstract

Extracellular vesicles (EVs) play key roles in glioblastoma (GBM) biology and represent novel sources of biomarkers that are detectable in the peripheral circulation. Despite this notionally non-invasive approach to assess GBM tumours in situ, a comprehensive GBM EV protein signature has not been described. Here, EVs secreted by six GBM cell lines were isolated and analysed by quantitative high-resolution mass spectrometry. Overall, 844 proteins were identified in the GBM EV proteome, of which 145 proteins were common to EVs secreted by all cell lines examined; included in the curated EV compendium (Vesiclepedia_559; http://microvesicles.org). Levels of 14 EV proteins significantly correlated with cell invasion (invadopodia production; r² > 0.5, p < 0.05), including several proteins that interact with molecules responsible for regulating invadopodia formation. Invadopodia, actin-rich membrane protrusions with proteolytic activity, are associated with more aggressive disease and are sites of EV release. Gene levels corresponding to invasion-related EV proteins showed that five genes (annexin A1, actin-related protein 3, integrin-β1, insulin-like growth factor 2 receptor and programmed cell death 6-interacting protein) were significantly higher in GBM tumours compared to normal brain in silico, with common functions relating to actin polymerisation and endosomal sorting. We also show that Cavitron Ultrasonic Surgical Aspirator (CUSA) washings are a novel source of brain tumour-derived EVs, demonstrated by particle tracking analysis, TEM and proteome profiling. Quantitative proteomics corroborated the high levels of proposed invasion-related proteins in EVs enriched from a GBM compared to low-grade astrocytoma tumour. Large-scale clinical follow-up of putative biomarkers, particularly the proposed survival marker annexin A1, is warranted.

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Annotated in Supplementary Table 1.

ANXA1, ITGA5, EGFR, FYN, CLIC1, RRAS, ARHGEF2, RAB1A, RAP1B, YBX1, KARS, NSF.

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Title: Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease
Authors: Duthika M. Mallawaaratchy
Susannah Hallal
Ben Russell
Linda Ly
Saeideh Ebrahimkhani
Heng Wei
Richard I. Christopherson
Michael E. Buckland
Kimberley L. Kaufman
Publication date: 01-01-2017
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2017
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2298-3

ACC 2024 Congress

Springer Medicine

Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease

Abstract

ACC 2024 Congress

Springer Medicine

Abstract

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