CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas.
Br J Cancer
; 131(2): 258-270, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38834745
ABSTRACT
BACKGROUND:
Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies.METHODS:
Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGGINV) and tumor core (HGGTC) cells.RESULTS:
pHGGINV cells were intrinsically more invasive than their matching pHGGTC cells. CSC profiling revealed co-positivity of CD133 and CD57 and identified CD57+CD133- cells as the most abundant CSCs in the invasive front. In addition to discovering a new order of self-renewal capacities, i.e., CD57+CD133- > CD57+CD133+ > CD57-CD133+ > CD57-CD133- cells, we showed that CSC hierarchy was impacted by their spatial locations, and the highest self-renewal capacities were found in CD57+CD133- cells in the HGGINV front (HGGINV/CD57+CD133- cells) mediated by NANOG and SHH over-expression. Direct implantation of CD57+ (CD57+/CD133- and CD57+/CD133+) cells into mouse brains reconstituted diffusely invasion, while depleting CD57+ cells (i.e., CD57-CD133+) abrogated pHGG invasion.CONCLUSION:
We revealed significantly increased invasive capacities in HGGINV cells, confirmed CD57 as a novel glioma stem cell marker, identified CD57+CD133- and CD57+CD133+ cells as a new cellular driver of pHGG invasion and suggested a new dual-mode hierarchy of HGG stem cells.
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Banco de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
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Neoplasias Encefálicas
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Antígenos CD57
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Antígeno AC133
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Glioma
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Invasividad Neoplásica
Límite:
Animals
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Child
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article