In vivo C6 glioma models: an update and a guide toward a more effective preclinical evaluation of potential anti-glioblastoma drugs

Abstract

Glioblastoma multiform (GBM) is the most common primary brain tumor with a poor prognosis and few therapeutic choices. In vivo, tumor models are useful for enhancing knowledge of underlying GBM pathology and developing more effective therapies/agents at the preclinical level, as they recapitulate human brain tumors. The C6 glioma cell line has been one of the most widely used cell lines in neuro-oncology research as they produce tumors that share the most similarities with human GBM regarding genetic, invasion, and expansion profiles and characteristics. This review provides an overview of the distinctive features and the different animal models produced by the C6 cell line. We also highlight specific applications of various C6 in vivo models according to the purpose of the study and offer some technical notes for more convenient/repeatable modeling. This work also includes novel findings discovered in our laboratory, which would further enhance the feasibility of the model in preclinical GBM investigations.

A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma

“…The blood–brain barrier in GBM exhibits higher permeability compared to healthy brain tissue, attributed to deficient formation, abnormal neovascularization, upregulated transporters, and downregulated tight junction proteins (Liebner et al 2018 ; Wu et al 2021 ). Furthermore, the C6 glioblastoma model is acclaimed for its fidelity in replicating human GBM pathology, including the pivotal aspect of inducing BBB breakdown (Pournajaf et al 2024 ). Research elucidates that the C6 tumor facilitates this breakdown via the secretion of factors like vascular endothelial growth factors (VEGF) and matrix metalloproteinases (MMPs), which collectively undermine the endothelial tight junctions and degrade the basal lamina, thereby compromising the barrier function (Feng et al 2022 ; Matsuno et al 2022 ).…”