Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment.
Animals
Antineoplastic Agents, Alkylating
/ pharmacology
Biopsy
Brain Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Plasticity
/ drug effects
Cohort Studies
Drug Resistance, Neoplasm
/ drug effects
Gene Expression Profiling
Glioblastoma
/ drug therapy
Humans
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells
/ drug effects
Temozolomide
/ pharmacology
Treatment Outcome
Tumor Microenvironment
/ drug effects
Xenograft Model Antitumor Assays
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 04 2019
16 04 2019
Historique:
received:
10
08
2018
accepted:
27
03
2019
entrez:
18
4
2019
pubmed:
18
4
2019
medline:
29
5
2019
Statut:
epublish
Résumé
The identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance have been challenged in brain tumors. Here we report that cells expressing CSC-associated cell membrane markers in Glioblastoma (GBM) do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. We show that phenotypic heterogeneity arises from non-hierarchical, reversible state transitions, instructed by the microenvironment and is predictable by mathematical modeling. Although functional stem cell properties were similar in vitro, accelerated reconstitution of heterogeneity provides a growth advantage in vivo, suggesting that tumorigenic potential is linked to intrinsic plasticity rather than CSC multipotency. The capacity of any given cancer cell to reconstitute tumor heterogeneity cautions against therapies targeting CSC-associated membrane epitopes. Instead inherent cancer cell plasticity emerges as a novel relevant target for treatment.
Identifiants
pubmed: 30992437
doi: 10.1038/s41467-019-09853-z
pii: 10.1038/s41467-019-09853-z
pmc: PMC6467886
doi:
Substances chimiques
Antineoplastic Agents, Alkylating
0
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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