Quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy. Dev Cell 2022 Jan 10;57(1):32-46.e8
Date
01/12/2022Pubmed ID
35016005Pubmed Central ID
PMC8820651DOI
10.1016/j.devcel.2021.12.007Scopus ID
2-s2.0-85123256377 (requires institutional sign-in at Scopus site) 58 CitationsAbstract
We test the hypothesis that glioblastoma harbors quiescent cancer stem cells that evade anti-proliferative therapies. Functional characterization of spontaneous glioblastomas from genetically engineered mice reveals essential quiescent stem-like cells that can be directly isolated from tumors. A derived quiescent cancer-stem-cell-specific gene expression signature is enriched in pre-formed patient GBM xenograft single-cell clusters that lack proliferative gene expression. A refined human 118-gene signature is preserved in quiescent single-cell populations from primary and recurrent human glioblastomas. The F3 cell-surface receptor mRNA, expressed in the conserved signature, identifies quiescent tumor cells by antibody immunohistochemistry. F3-antibody-sorted glioblastoma cells exhibit stem cell gene expression, enhance self-renewal in culture, drive tumor initiation and serial transplantation, and reconstitute tumor heterogeneity. Upon chemotherapy, the spared cancer stem cell pool becomes activated and accelerates transition to proliferation. These results help explain conventional treatment failure and lay a conceptual framework for alternative therapies.
Author List
Xie XP, Laks DR, Sun D, Ganbold M, Wang Z, Pedraza AM, Bale T, Tabar V, Brennan C, Zhou X, Parada LFAuthor
Daochun Sun PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBrain Neoplasms
Cell Cycle
Cell Division
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Survival
Cell Transformation, Neoplastic
Gene Expression
Gene Expression Regulation, Neoplastic
Glioblastoma
Heterografts
Humans
Mice
Neoplasm Invasiveness
Neoplasm Recurrence, Local
Neoplastic Stem Cells
Transcriptome
