Poster Presentation Australasian Extracellular Vesicles Conference 2018

Evaluating the role of invadopodia in glioma invasion and response to therapeutics (#64)

Clarissa A Whitehead 1 , Andrew P Morokoff 1 , Rodney B Luwor 1 , Theo Mantamadiotis 1 , Andrew H Kaye 1 , Stanley S Stylli 1
  1. The University of Melbourne, Parkville, VIC, Australia

Glioblastoma (GBM) is the most prevalent and aggressive form of glioma and is currently incurable, with 5.5% of GBM patients surviving 5 years post-diagnosis. As median survival remains low, at just 15 months with standard treatment consisting of with surgical resection, followed by radiotherapy (RT) and Temozolomide (TMZ), there is an urgent need for novel therapies to improve patient outcome.

Evidence suggests that poor survival may result from a treatment-induced invasive phenotype in surviving tumour cells. We have shown that this invasiveness can be mediated through membrane localized protrusive structures called invadopodia. Extracellular vesicles (EVs) may facilitate this invasive process and as such it is possible that EVs may be involved the activity of invadopodia in GBM.

Utilizing several different assays, we examined the effect of RT and TMZ on invadopodia activity in GBM cells. We observed that a single dose of RT and TMZ treatment results in an increase in invadopodia matrix degrading activity that is also maintained after long term treatment. We have also successfully isolated EVs from cultured GBM cells, and detected that single-dose and long-term treatment with RT/TMZ increases the number of EVs that are secreted compared to untreated cells.

Therefore, the current therapeutic approach of RT and TMZ appears to increase the matrix degrading activity of invadopodia and EV secretion in GBM cells surviving therapy. Continued research will allow further elucidation of the combined role of invadopodia and EVs in GBM invasion, as well as investigating novel therapeutic strategies to counteract their activity.