Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone.
Children
Diffuse infiltrating pontine glioma
Diffuse midline glioma
Glioblastoma
Glioma stem cells
High-grade glioma
Histone
Pediatric
Slow-cycling cells
Subventricular zone
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
16 06 2023
16 06 2023
Historique:
received:
07
03
2023
accepted:
20
05
2023
medline:
19
6
2023
pubmed:
17
6
2023
entrez:
16
6
2023
Statut:
epublish
Résumé
Pediatric high-grade gliomas (pHGG) are brain tumors occurring in children and adolescents associated with a dismal prognosis despite existing treatments. Therapeutic failure in both adult and pHGG has been partially imputed to glioma stem cells (GSC), a subset of cancer cells endowed with stem-like cell potential and malignant, invasive, adaptative, and treatment-resistant capabilities. Whereas GSC have largely been portrayed in adult tumors, less information has been provided in pHGG. The aim of our study was to comprehensively document the stem-like capacities of seven in-use pediatric glioma cell cultures (Res259, UW479, SF188, KNS42, SF8628, HJSD-DIPG-007 and HJSD-DIPG-012) using parallel in vitro assays assessing stem cell-related protein expression, multipotency, self-renewal and proliferation/quiescence, and in vivo investigation of their tumorigenicity and invasiveness. Data obtained from in vitro experiments revealed glioma subtype-dependent expression of stem cell-related markers and varying abilities for differentiation, self-renewal, and proliferation/quiescence. Among tested cultures, DMG H3-K27 altered cultures displayed a particular pattern of stem-like markers expression and a higher fraction of cells with self-renewal potential. Four cultures displaying distinctive stem-like profiles were further tested for their ability to initiate tumors and invade the brain tissue in mouse orthotopic xenografts. The selected cell cultures all showed a great tumor formation capacity, but only DMG H3-K27 altered cells demonstrated a highly infiltrative phenotype. Interestingly, we detected DMG H3-K27 altered cells relocated in the subventricular zone (SVZ), which has been previously described as a neurogenic area, but also a potential niche for brain tumor cells. Finally, we observed an SVZ-induced phenotypic modulation of the glioma cells, as evidenced by their increased proliferation rate. In conclusion, this study recapitulated a systematic stem-like profiling of various pediatric glioma cell cultures and call to a deeper characterization of DMG H3-K27 altered cells nested in the SVZ.
Identifiants
pubmed: 37328883
doi: 10.1186/s40478-023-01586-x
pii: 10.1186/s40478-023-01586-x
pmc: PMC10276389
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
96Informations de copyright
© 2023. The Author(s).
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