Detalle de: ANGI-06. CHARACTERISATION OF INVASION OF HUMAN BRAIN TUMOUR INITIATING CELLS IN HUMAN GLIOBLASTOMA

INTRODUCTION A main pathophysiological feature of glioblastoma (GBM) is widespread invasion of the brain parenchyma, rendering localized therapies ineffective. In addition, brain tumour initiating cells (BTIC) may repopulate the tumour site after initially effective treatments. Thus, the invasive tumour cell fraction is a strategic prime target for early anti-invasion therapies. METHODS With organotypic brain slice cultures (OBSC) and single cell RNA expression analysis, we established a novel integrated approach to investigate the expression profile of invasion leading cells. In comparison, we used long-term intravital imaging through a cranial window to analyse the interaction of invasive with non-invasive cells and the microenvironment in vivo. RESULTS The in situ OBSC model allowed us to monitor human BTIC cell invasion in real time. Invasive cells (that we determined leader cells) emerge from the initial cell population and drive invasion into the surrounding tissue. Those cells differ in morphology and behaviour from stationary cells, which remain at the implantation site. Leader cells have a markedly distinct gene expression pattern in comparison to stationary cells. The leader cell-specific expression signature is currently verified in patient tumour biopsies and in the cranial window model. Updated results will be presented at the SNO meeting. OUTLOOK We show that invasive leader cells in GBM have a specific functional and molecular profile. We hypothesize that a deep characterization of these cells in respect to their interaction with and response to the microenvironment will shed light on the chronology of one of the gliomagenesis milestones, namely invasion.