Abstract
Abstract The main obstacles for effective treatment of Glioblastoma (GBM) are high invasiveness and heterogeneity. Each GBM tumor is composed of multiple genetically distinct subpopulations of Glioma Stem Cells (GSCs), exhibiting high cell plasticity affecting their invasive and proliferative properties. Treatment interventions and changes in microenvironment force GSCs to adapt through gene expression that supports therapeutic resistance. Expression level of the surface receptor CD97/ADRGE5 positively correlates with poor GBM patient prognosis, but its role in this tumor has not been elucidated. Here, we examined the function of CD97 in primary GSCs derived from five GBM tumors, which belong to three major genetic subtypes. We manipulated CD97 levels in these GSCs by knockdown and overexpression and analyzed the following: (i) expression of stem and subtype markers, (ii) in vitro invasive properties, (iii) cell proliferation, (iv) expression of the key proteins that regulate GSCs cellular state and influence their adaptive behavior. Our data showed that CD97 knockdown in GSCs of mesenchymal and classical subtype reduced their invasion rate in vitro. CD97 signaling positively affected expression of Epidermal Growth Factor Receptor, the main driver of astrocyte-like fate in GSCs and changed the expression of the astrocytic marker GFAP. Finally, we discovered a possible link between CD97 and expression of transcription factor Sox2, the key regulator of the endothelial-to-mesenchymal transition process that plays a crucial role in initiation of cancer cell invasion. Citation Format: Tatiana I. Slepak, Daniel G. Eichberg, Ana L. Pascoini, Ricardo J. Komotar, Michael E. Ivan. Adhesion GPCR CD97/ADGRE5 facilitates invasion in patient-derived glioma stem cells and induces changes in EGFR and Sox2 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2876.