CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas
Menée à l'aide de xénogreffes de gliomes de haut grade, cette étude identifie un sous-type de cellules souches cancéreuses qui expriment l'antigène CD57 et favorisent l'invasion des gliomes diffus de "type pédiatrique"
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.
British Journal of Cancer , article en libre accès, 2024