Glioblastoma (GBM) is the most aggressive brain cancer. To model GBM in research, orthotopic brain tumor models, including syngeneic models like GL261 and genetically engineered mouse models like TRP, are used. In longitudinal studies, tumor growth and the treatment response are typically tracked with in vivo imaging, including bioluminescence imaging (BLI), which is quick, cost-effective, and easily quantifiable. However, BLI requires luciferase-tagged cells, and recent studies indicate that the luciferase gene can elicit an immune response, leading to tumor rejection and experimental variation. We sought to optimize the engraftment of two luciferase-expressing GBM models, GL261 Red-FLuc and TRP-mCherry-FLuc, showing differences in tumor take, with GL261 Red-FLuc cells requiring immunocompromised mice for 100% engraftment. Immunohistochemistry and MRI revealed distinct tumor characteristics: GL261 Red-FLuc tumors were well-demarcated with densely packed cells, high mitotic activity, and vascularization. In contrast, TRP-mCherry-FLuc tumors were large, invasive, and necrotic, with perivascular invasion. Quantifying the tumor volume using the HALO®AI analysis platform yielded results comparable to manual measurements, providing a standardized and efficient approach for the reliable, high-throughput analysis of luciferase-expressing tumors. Our study highlights the importance of considering tumor engraftment when using luciferase-expressing GBM models, providing insights for preclinical research design.
胶质母细胞瘤（GBM）是最具侵袭性的脑癌。在研究中为模拟GBM，常使用原位脑肿瘤模型，包括GL261等同基因模型和TRP等基因工程小鼠模型。在纵向研究中，通常通过体内成像技术追踪肿瘤生长和治疗反应，其中生物发光成像（BLI）具有快速、经济、易于量化的特点。然而，BLI需要使用荧光素酶标记的细胞，近期研究表明荧光素酶基因可能引发免疫反应，导致肿瘤排斥并引起实验变异。本研究旨在优化两种表达荧光素酶的GBM模型（GL261 Red-FLuc和TRP-mCherry-FLuc）的移植效果，发现两者肿瘤形成率存在差异：GL261 Red-FLuc细胞需在免疫缺陷小鼠中才能实现100%移植成功率。免疫组化和磁共振成像显示两类肿瘤具有不同特征：GL261 Red-FLuc肿瘤边界清晰，细胞排列密集，具有高有丝分裂活性和血管化特征；而TRP-mCherry-FLuc肿瘤则呈现体积大、侵袭性强、伴有坏死及血管周围浸润的特点。通过HALO®AI分析平台量化肿瘤体积的结果与人工测量具有可比性，为表达荧光素酶的肿瘤提供了标准化、高效的可信高通量分析方法。本研究强调使用荧光素酶表达GBM模型时需重视肿瘤移植特性，为临床前研究设计提供了重要参考。
肿瘤(癌症)患者之家