Molecular characteristics of single patient-derived glioma stem-like cells from primary and recurrent glioblastoma.

Abstract

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.

• Authors: Jia Shi, Xuchen Dong, Wei Han, Peng Zhou, Liang Liu, Haiyang Wang, Qianqian Jiang, Haoran Li, Shan Cheng, Suwen Li, Jiaqi Yuan, Zhiyuan Qian, Jun Dong
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 33 Issue 1 Pg. e381-e388 (01 01 2022) ISSN: 1473-5741 [Electronic] England
• PMID: 34419956 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Chemical References

• Temozolomide

Topics

• Animals
• Brain Neoplasms (genetics)
• Cell Proliferation (physiology)
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation
• Glioma (genetics, pathology)
• Humans
• Kaplan-Meier Estimate
• Male
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Recurrence, Local
• Neoplastic Stem Cells (pathology)
• Phenotype
• Temozolomide (pharmacology)
• Xenograft Model Antitumor Assays
• Mice