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Molecular characteristics of single patient-derived glioma stem-like cells from primary and recurrent glioblastoma.
Anti-Cancer Drugs ( IF 2.3 ) Pub Date : 2021-08-20 , DOI: 10.1097/cad.0000000000001217
Jia Shi 1, 2 , Xuchen Dong 1 , Wei Han 3 , Peng Zhou 2 , Liang Liu 1 , Haiyang Wang 1 , Qianqian Jiang 1 , Haoran Li 1 , Shan Cheng 1 , Suwen Li 1 , Jiaqi Yuan 1 , Zhiyuan Qian 1 , Jun Dong 1
Affiliation  

Glioblastoma has high recurrence, while the sensitivity of recurrent glioblastoma to chemotherapy is lower than that of primary glioblastoma. Moreover, there is no standardized treatment for recurrent glioblastoma. Unfortunately, the biological mechanism of recurrent glioblastoma is still unclear, and there are few related studies. We compared the phenotypes of clinical glioblastoma specimens, in-vitro cultured glioma stem-like cells (GSCs) and patient-derived xenograft tumor (PDX) models to explore the molecular genetic characteristics of primary and recurrent glioblastoma from the same patient. In vitro, SU5-2, GSCs derived from recurrent glioblastoma specimens, had stronger proliferative activity and self-renewal ability. Meanwhile, SU5-2 was more resistant to temozolomide and invasive than SU5-1, which derived from primary glioblastoma specimens. Further analysis of the expression of costimulatory molecules showed that the expression of B7-H1, B7-H2 and B7-H3 of SU5-2 were upregulated. In vivo, Kaplan-Meier survival curve analysis showed that the median survival of the recurrent PDX group was worse. The results of gene detection in vitro, PDX model and clinical samples were consistent. Our results showed that the GSCs based on glioblastoma specimens and the PDX models could replicate the main molecular genetic characteristics of original tumors, which provided a reliable experimental platform for both tumor translation kinds of research and screening of molecular therapeutic targets.

中文翻译:

来自原发性和复发性胶质母细胞瘤的单个患者来源的胶质瘤干细胞的分子特征。

胶质母细胞瘤复发率高,而复发性胶质母细胞瘤对化疗的敏感性低于原发性胶质母细胞瘤。此外,对于复发性胶质母细胞瘤没有标准化的治疗方法。遗憾的是,复发性胶质母细胞瘤的生物学机制尚不清楚,相关研究也很少。我们比较了临床胶质母细胞瘤标本、体外培养的胶质瘤干样细胞(GSC)和患者来源的异种移植肿瘤(PDX)模型的表型,以探索同一患者的原发性和复发性胶质母细胞瘤的分子遗传特征。在体外,来自复发性胶质母细胞瘤标本的GSCs SU5-2具有更强的增殖活性和自我更新能力。同时,SU5-2比源自原发性胶质母细胞瘤标本的SU5-1对替莫唑胺具有更强的耐药性和侵袭性。进一步分析共刺激分子的表达量发现SU5-2的B7-H1、B7-H2和B7-H3的表达量上调。在体内,Kaplan-Meier生存曲线分析显示,复发PDX组的中位生存期较差。体外基因检测结果、PDX模型与临床样本结果一致。我们的研究结果表明,基于胶质母细胞瘤标本和PDX模型的GSC可以复制原始肿瘤的主要分子遗传特征,这为肿瘤转化类研究和分子治疗靶点筛选提供了可靠的实验平台。
更新日期:2021-08-20
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