文章：

基于多区域采样的胶质瘤干细胞功能与分子异质性研究

Functional and Molecular Heterogeneity in Glioma Stem Cells Derived from Multiregional Sampling

原文发布日期：13 December 2023

DOI: 10.3390/cancers15245826

类型: Article

开放获取: 是

英文摘要：

Glioblastoma (GBM) is an aggressive and highly heterogeneous primary brain tumor. Glioma stem cells represent a subpopulation of tumor cells with stem cell traits that are presumed to be the cause of tumor relapse. There exists complex tumor heterogeneity in drug sensitivity patterns between glioma stem cell (GSC) cultures derived from different patients. Here, we describe that heterogeneity also exists between GSC cultures derived from multiple biopsies within a single tumor. From biopsies harvested within spatially distinct regions representing the entire tumor mass, we established seven GSC cultures and compared their stem cell properties, mutations, gene expression profiles, and drug sensitivity patterns against 115 different anticancer drugs. The results were compared to 14 GSC cultures derived from other patients. Between the multiregional-derived GSC cultures, we observed only minor differences in their phenotype, proliferative capacity, and global gene expression. Further, they displayed intratumoral heterogeneity in mutational profiles and sensitivity patterns to anticancer drugs. This heterogeneity, however, did not exceed the extensive heterogeneity found between GSC cultures derived from other GBM patients. Our results suggest that the use of GSC cultures from one single focal biopsy may underestimate the overall complexity of the GSC population and display the importance of including GSC cultures reflecting the entire tumor mass in drug screening strategies.

摘要翻译： 

胶质母细胞瘤是一种侵袭性强且高度异质性的原发性脑肿瘤。胶质瘤干细胞作为具有干细胞特性的肿瘤细胞亚群，被认为是导致肿瘤复发的根源。不同患者来源的胶质瘤干细胞培养物在药物敏感性模式上存在复杂的肿瘤异质性。本研究发现，这种异质性同样存在于同一肿瘤内多区域活检样本来源的胶质瘤干细胞培养物之间。通过采集代表整个肿瘤空间分布特征的不同区域活检样本，我们建立了七株胶质瘤干细胞培养系，并系统比较了它们的干细胞特性、突变谱、基因表达谱以及对115种不同抗癌药物的敏感性模式。研究结果进一步与来自其他患者的14株胶质瘤干细胞培养系进行对比分析。研究发现，多区域来源的胶质瘤干细胞培养系在表型特征、增殖能力和整体基因表达谱方面仅存在微小差异。然而，这些培养系在突变谱和抗癌药物敏感性模式上表现出显著的瘤内异质性。值得注意的是，这种瘤内异质性并未超过不同胶质母细胞瘤患者来源培养系间存在的广泛异质性。本研究结果表明，仅使用单一局灶活检样本建立的胶质瘤干细胞培养模型可能低估胶质瘤干细胞群体的整体复杂性，并凸显了在药物筛选策略中纳入能反映完整肿瘤特征的胶质瘤干细胞培养模型的重要性。

原文链接：

Functional and Molecular Heterogeneity in Glioma Stem Cells Derived from Multiregional Sampling