Variable IL13Rα2 Expression Across Glioblastoma Models and Tumor Regions

Abstract

Background: Interleukin-13 Receptor alpha 2 (IL13Rα2) is an attractive therapeutic target for glioblastoma because of its limited expression in normal brain tissue and overexpression in many tumors. However, the spatial heterogeneity of glioblastoma and limitations of conventional culture models may contribute to the inconsistent translation of IL13Rα2-targeted therapies. This study evaluated IL13Rα2 expression across multiple in vitro glioblastoma models and spatially resolved patient tumors. Methods: IL13Rα2 mRNA and protein expression levels were measured across two-dimensional and three-dimensional glioblastoma culture models, including commercial cell lines (U87MG and T98G), and patient-derived neurospheres. Spatial expression patterns were also characterized using Ivy Glioblastoma Atlas Project. Results: IL13Rα2 expression was highly dependent on glioblastoma model system, with substantial variability observed across commercial cell lines, patient-derived neurospheres, and three-dimensional cultures. Spatial transcriptomic analysis identified significant enrichment of IL13Rα2 expression within perinecrotic tumor regions relative to the leading edge, infiltrating tumor, and cellular tumor. Conclusions: The heterogeneous nature of glioblastoma highlights the limitations of current in vitro modeling and the importance of considering spatial expression patterns when developing IL13Rα2-targeted therapies.