Department of Pharmaceutical Sciences, College of Pharmacy University of Kentucky, Lexington, KY, USA.
Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA.
BMC Cancer. 2022 Aug 3;22(1):844. doi: 10.1186/s12885-022-09910-9.
Glioblastoma (GBM) is one of the deadliest cancers. Treatment options are limited, and median patient survival is only several months. Translation of new therapies is hindered by a lack of GBM models that fully recapitulate disease heterogeneity. Here, we characterize two human GBM models (U87-luc2, U251-RedFLuc). In vitro, both cell lines express similar levels of luciferase and show comparable sensitivity to temozolomide and lapatinib exposure. In vivo, however, the two GBM models recapitulate different aspects of the disease. U87-luc2 cells quickly grow into large, well-demarcated tumors; U251-RedFLuc cells form small, highly invasive tumors. Using a new method to assess GBM invasiveness based on detecting tumor-specific anti-luciferase staining in brain slices, we found that U251-RedFLuc cells are more invasive than U87-luc2 cells. Lastly, we determined expression levels of ABC transporters in both models. Our findings indicate that U87-luc2 and U251-RedFLuc GBM models recapitulate different aspects of GBM heterogeneity that need to be considered in preclinical research.
胶质母细胞瘤（GBM）是最致命的癌症之一。治疗方案有限，中位患者生存期仅为数月。由于缺乏完全再现疾病异质性的 GBM 模型，新疗法的转化受到阻碍。在这里，我们描述了两种人类 GBM 模型（U87-luc2、U251-RedFLuc）。在体外，两种细胞系表达相似水平的荧光素酶，并对替莫唑胺和拉帕替尼暴露表现出相似的敏感性。然而，在体内，这两种 GBM 模型再现了疾病的不同方面。U87-luc2 细胞迅速生长成大而界限分明的肿瘤；U251-RedFLuc 细胞形成小而高度侵袭性的肿瘤。使用一种新方法基于在脑切片中检测肿瘤特异性抗荧光素酶染色来评估 GBM 的侵袭性，我们发现 U251-RedFLuc 细胞比 U87-luc2 细胞更具侵袭性。最后，我们确定了两种模型中 ABC 转运蛋白的表达水平。我们的研究结果表明，U87-luc2 和 U251-RedFLuc GBM 模型再现了 GBM 异质性的不同方面，这些方面在临床前研究中需要考虑。
