A multiparametric perspective on C6 and F98 cell lines in orthotopic rat models for glioblastoma research

Glioblastoma remains a significant healthcare challenge due to its aggressiveness and poor prognosis, underscoring the urgent need for innovative approaches to tackle this disease. While there is a growing emphasis on the use of in vitro models for these developments, animal models continue to play a pivotal role, as they provide insights into the complex tumor microenvironment (TME) and host interactions that in vitro systems cannot fully replicate. However, selecting the appropriate animal model based on the research question is fundamental to ensure the reliability and translational potential of preclinical findings. Advanced neuroimaging techniques, particularly magnetic resonance imaging (MRI) and spectroscopy (MRS), offer unique advantages for the in vivo characterization of glioblastoma models. These techniques offer comprehensive morphological, functional, and metabolomic insights, enabling the evaluation of critical tumor features, such as vascular permeability, infiltrative capacity, or metabolism, among others. In this study, different glioblastoma models were generated by orthotopic implantation of two widely used glioblastoma cell lines, C6 and F98, in Fischer, Sprague Dawley, and Wistar rats and characterized by multiparametric MRI, MRS, along with histological analysis. Results revealed that the F98-Fischer model closely mimics human glioblastoma regarding vascular permeability, infiltrative growth, and key metabolic hallmarks. In contrast, the C6-Wistar model, while exhibiting similarities in permeability and metabolism, lacked invasive growth. Moreover, the two cell lines showed different responses to the host environment, with F98 consistently forming infiltrative tumors across rat strains, while C6 showed variability in tumor growth patterns, suggesting a greater dependence on the host microenvironment. These findings underscore the complex interplay between cell line genetics and host factors in defining tumor phenotype, emphasizing the importance of considering host-tumor interactions in glioblastoma research.