Poster Presentation Australasia Extracellular Vesicles Conference 2017

Cavitron Ultrasonic Surgical Aspirates are Novel Sources of Glioblastoma-derived Extracellular Vesicles   (#49)

Susannah S.H Hallal 1 2 , Duthika D.M Mallawaaratchy 3 , Ben B.R Russel 1 2 , Saeideh S.E Ebrahim Khani 1 2 , Heng H.W. Wei 2 4 , Michael M.B Buckland 1 2 4 , Kimberley K.K Kaufman 2 3 4
  1. Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
  2. Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
  3. Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia
  4. Neuropathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Glioblastoma (GBM), or stage IV astrocytoma, is the most common and lethal primary brain tumour in adults. GBM carries an exceedingly poor prognosis due to its aggressive, invasive and recurrent nature. EVs are 30-1000 nm membranous vesicles released by all cells and contain molecules that reflect their cell of origin. Studies have showed that extracellular vesicles (EV) play key roles in GBM biology and represent novel biomarker reservoirs.

Recently, the Kaufman lab described the most comprehensive in vitro GBM-EV proteome signature to date  [1]. EVs were isolated from six established GBM cell-lines and analysed by quantitative high resolution mass spectrometry. A total of 844 proteins were identified, of which 145 were common to the GBM-EV from all six cell-lines. Levels of 14 GBM-EV proteins significantly correlated to GBM cell invasiveness. We aim to translate this in vitro GBM-EV protein signature to clinical specimens in order to describe new biomarkers that are predictive of GBM progression and invasion.

We have identified and characterised Cavitron Ultrasonic Surgical Aspirate (CUSA) fluids as novel and rich sources of brain tumour-EVs, demonstrated by transmission electron microscopy (TEM), nanosight particle tracking analysis (NTA) and label-free quantitative mass spectrometry analysis. Quantitative proteomic analysis of enriched CUSA-EV from high-grade and low-grade gliomas showed that there was greater than 70% coverage of the in vitro GBM-EV proteome signature in CUSA-EV. In addition, levels of the proposed invasion-related markers were significantly higher in EV from high-grade gliomas in comparison to lower-grade gliomas.

  1. Mallawaaratchy, D.M., Hallal S. et al., Comprehensive proteome profiling of glioblastoma-derived extracellular vesicles identifies markers for more aggressive disease. Journal of Neuro-Oncology, 2016: p. 1-12.