Quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy Journal Article


Authors: Xie, X. P.; Laks, D. R.; Sun, D.; Ganbold, M.; Wang, Z.; Pedraza, A. M.; Bale, T.; Tabar, V.; Brennan, C.; Zhou, X.; Parada, L. F.
Article Title: Quiescent human glioblastoma cancer stem cells drive tumor initiation, expansion, and recurrence following chemotherapy
Abstract: 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. © 2021 Elsevier Inc.
Keywords: temozolomide; recurrence; glioblastoma; quiescence; heterogeneity; cancer stem cells; chemoresistance; single-cell rna sequencing; f3 receptor
Journal Title: Developmental Cell
Volume: 57
Issue: 1
ISSN: 1534-5807
Publisher: Cell Press  
Date Published: 2022-01-10
Start Page: 32
End Page: 46.e8
Language: English
DOI: 10.1016/j.devcel.2021.12.007
PROVIDER: scopus
PUBMED: 35016005
PMCID: PMC8820651
DOI/URL:
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Viviane S Tabar
    225 Tabar
  2. Cameron Brennan
    226 Brennan
  3. Alicia Maria Pedraza
    26 Pedraza
  4. Luis F Parada
    31 Parada
  5. Zilai Wang
    9 Wang
  6. Daochun Sun
    18 Sun
  7. Xuanhua Xie
    15 Xie
  8. Dan R Laks
    7 Laks
  9. Tejus Bale
    122 Bale