Invadopodia small extracellular vesicles glioblastoma

The therapeutic efficacy of radiotherapy and chemotherapy with temozolomide (TMZ) for glioblastoma (GBM) is currently limited by the augmented invasive abilities of GBM cells that survive treatment, however the underlying mechanisms remain poorly understood. Due to their ability of transporting oncogenic material between cells, small extracellular vesicles (sEVs) have emerged as key mediators of tumour progression and resistance to treatment. Here, we report that sEVs secreted by GBM cells may facilitate tumour invasion through their ability to promote the formation and activity of actin-rich protrusions known as invadopodia, and that this may be further enhanced following exposure to radio-chemotherapeutic treatment. Furthermore, proteomic analysis of GBM cells exposed to this treatment revealed an increased abundance of invasion-related proteins (including adhesion, cytoskeletal, and membrane trafficking proteins), whilst sEVs were instead enriched in invadopodia-related signalling cargo proteins. Collectively, this work highlights the contributing role of invadopodia and sEVs to the pro-invasive abilities of GBM cells that survive radio-chemotherapeutic treatment.