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

• Published in: British journal of cancer Vol. 131; no. 2; pp. 258 - 270
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.07.2024; Nature Publishing Group
• Subjects: 631/67/2332; 631/67/70; 631/67/71; Biomedical and Life Sciences; Biomedicine; Cancer Research; CD57 antigen; Cell self-renewal; Drug Resistance; Epidemiology; Glioma; Glioma cells; Invasiveness; Molecular Medicine; Oncology; Overexpression; Pediatrics; Stem cells
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-024-02724-5

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.