TMOD-45. Immune Competent Glioblastoma Models for Therapeutic Translation

作者：Loizos Michaelides, M.W. Julian, Beatriz Fernandez Gil, Paula Schiapparelli, Vanessa K. Jones, Mieu Brooks, Susan Arnold, Stephany Y. Tzeng, L. Pluhar, Jordan J. Green, Alfredo Quiñones-Hinojosa · 发表于：Neuro-Oncology · 年份：2025 · DOI：10.1093/neuonc/noaf201.1918 · 研究领域：Veterinary Oncology Research、Virus-based gene therapy research、Cancer Research and Treatments

Abstract Spontaneously arising canine high-grade gliomas (cHGG) offer a clinically relevant model for human glioblastoma, sharing conserved histopathological, genetic, and immunological traits. We established two cHGG cell lines and two canine adipose-derived mesenchymal stem cell (cAMSC) lines, and immune-competent 3D cHGG organoid models. Immunoblotting of cHGG cell lines showed that these models exhibit hallmark GBM features including SOX2, Nestin, GFAP, and activation of PI3K/AKT and p53 pathways. Given the established cytotoxic and differentiation-inducing effects of BMP4 in human GBM cell lines, we evaluated whether our canine glioma models recapitulate these responses to assess their translational relevance. BMP4 treatment of cHGG cells induced significant cytotoxicity and reduced migration, accompanied by downregulation of SOX2 and Nestin, upregulation of GFAP, and suppression of CDK6 and phospho-AKT—hallmarks of reduced stemness and astrocytic differentiation. In human-derived GBM cells, BMP4 enhanced radiosensitivity, likely via differentiation and depletion of therapy-resistant stem-like populations. Our cHGG models mirrored these molecular responses, suggesting a conserved BMP4 signaling axis in canine glioma. Quantitative phase imaging showed that BMP4 treatment was non-toxic to cAMSCs and did not impair their migration, supporting the feasibility of engineering cAMSC-BMP4 for therapeutic delivery. Observed molecular traits in canine and human gliomas—including m...