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- Title
CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas.
- Authors
Qi, Lin; Du, Yuchen; Huang, Yulun; Kogiso, Mari; Zhang, Huiyuan; Xiao, Sophie; Abdallah, Aalaa; Suarez, Milagros; Niu, Long; Liu, Zhi-gang; Lindsay, Holly; Braun, Frank K.; Stephen, Clifford; Davies, Peter J.; Teo, Wan Yee; Adenkunle, Adesina; Baxter, Patricia; Su, Jack MF.; Li, Xiao-Nan
- 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.
- Publication
British Journal of Cancer, 2024, Vol 131, Issue 2, p258
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1038/s41416-024-02724-5