CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas

期刊论文
发表日期：

2024年6月4日

查看全文

Lin Qi,
Yuchen Du,
Yulun Huang,
Mari Kogiso,
Huiyuan Zhang,
Sophie Xiao,
Aalaa Abdallah,
Milagros Suarez,
Long Niu,
Zhi-gang Liu,
Holly Lindsay,
Frank K. Braun,
Clifford Stephen,
Peter J. Davies,
Wan Yee Teo,
Adesina Adenkunle,
Patricia Baxter,
Jack MF. Su,
Xiao-Nan Li

摘要

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 (HGG^INV) and tumor core (HGG^TC) cells.

Results

pHGG^INV cells were intrinsically more invasive than their matching pHGG^TC 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 HGG^INV front (HGG^INV/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 HGG^INV 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.