Abstract 1217: Modelling GBM-vasculature interaction on chip

Abstract The tumor microenvironment (TME) in glioblastoma (GBM) is remarkably intricate, characterized by its dynamic nature and high heterogeneity that significantly influence tumor progression and treatment resistance. The heterogeneous TME comprises of blood vessels, immune cells, neurons, and the blood-brain barrier (BBB) presenting distinct tumor compartments that influence the tumor behavior. A recent classification based on the heterogeneous TME identified three distinct subtypes TMELow, TMEMed, and TMEHigh distinguished by varying endothelial and immune cell populations. This study explores the complex interactions between glioblastoma (GBM) and its tumor microenvironment (TME), focusing specifically on the blood-brain barrier (BBB) and vascular compartment. To evaluate GBM's impact on the BBB, a compartmentalized model was developed that prevents direct cell-to-cell contact, allowing the observation of paracrine signaling. Using this model, distinct effects were identified across different GBM cell lines: one cell line caused significant BBB permeability with low transendothelial electrical resistance (TEER) values, while another had minimal impact on barrier integrity. To further investigate GBM-BBB interactions, a vascular network model incorporating brain endothelial cells, stromal cells and GBM cells within an extracellular matrix was developed. This model revealed consistent differences between the cell lines, aligning with the initial findings and reflected in endothelial cell morphology and vascular network density. Analysis of cytokines secreted by the GBM cell lines provided further insights into the observed changes in vascular organization. Ongoing investigation aims to use patient derived cells in this model to pick up interpatient variability and specifically look at the differences between the TME subtypes. This approach allows for the in vitro modelling and characterization of GBM TME subtypes and potentially the identification of novel druggable targets in the GBM TME. Citation Format: Promise Emeh, Kevin Jimenez-Cowell, Martine Lamfers, Clemens Dirven, Nick Saites, Todd Burton, Karla Queiroz. Modelling GBM-vasculature interaction on chip [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1217.