GBM cells from the tumour mass versus the subventricular zone: molecular and functional characterisation

Life expectancy after diagnosis of glioblastoma (GBM) remains poor even with the best available treatment. This catastrophic survival is the direct consequence of systematic tumour recurrence.
It has previously been demonstrated that the subventricular zone (SVZ, a neurogenic niche of the adult central nervous system) attracts and harbours GBM cells, expressing stem cell biomarkers that act like glioblastoma-initiating cells. These cells hosted in the SVZ may be responsible for tumour recurrence. To better understand the difference between cells from the tumour mass (TM) and those migrating to the SVZ, this project will focus on two axes. First, a proteomic and transcriptomic approach will be used to identify one or more biomarkers that might help to establish if recurrences originate from the TM or the SVZ. The second aim of the project is to compare these two populations of cells from a functional point of view.
Some functional differences have already been observed: cells derived from SVZ form more spheroids than those derived from TM (1). U87MG cells from SVZ also form tumours more easily in mice compared to cells derived from the TM (2). However, preliminary results in chemo- and radioresistance assays on the cultured cells (U87MG) do not show significant differences between the two populations. Therefore, it might be the SVZ environment that plays a key role in therapeutic resistance, rather than intrinsic biological differences of cells from the TM versus the SVZ.