Dissecting Glioma Invasiveness in a 3D-Organotypic Model

Abstract

Diffuse brain infiltration by tumor cells is a hallmark of glioma. Molecular mechanisms of brain invasion are poorly understood due to the difficulty to model this process in culture. A new study published in Cell Reports developed a three-dimensional organotypic model and identified interferon regulatory factor 3 (IRF3) as repressor of glioma invasion.

The multifaceted mechanisms of malignant glioblastoma progression and clinical implications

“…Collagens were observed at tumor boundaries in focal mouse GBM xenografts but in invasive xenografts, were found to be interspersed with tumor cells to form a complex [ 53 ]. Additional 3D ECM/tumor cell in vitro systems suggest collagen is indispensable for matrix preparations in assays of tumor cell behavior, providing circumstantial but functional evidence for a role in tumor growth and invasion [ 54 , 55 ]. In summary, invasive GBM cells remodel the tumor microenvironment by upregulating or downregulating the synthesis of ECM components and vascular basement membrane proteins to generate a more hospitable environment for tumor migration and infiltration (Fig.…”

A grasp on GFAP in Glioma

“…Ex vivo organotypic brain slices are commonly used in glioma research De Boüard et al 2002;Xu et al 2016;S. Jung et al 2002;Codega and Mellinghoff 2017), as they provide a more high throughput alternative to in vivo studies, whilst maintaining a relevant brain microenvironment (de Gooijer et al 2018). The novel combination with whole-mount immunofluorescent staining allows high-resolution imaging of cells in the tumour core and the mouse brain tissue and is a successful strategy to systematically quantify the invasive capacities of glioma cells.…”