Pediatric high-grade glioma (pHGG) is one of the deadliest cancers, with an extremely poor prognosis in children and no effective treatments available at diagnosis. Neural progenitor cells (NPCs), precursors to various neural lineages, have been proposed as the potential cell-of-origin for these aggressive brain tumours. NPCs are highly proliferative and can secrete factors that promote the growth and differentiation of neighboring cells. Strikingly, clinical studies have shown that gliomas in adult have a significantly higher recurrence rate when the tumor is located closer to the subventricular zone, a region which is enriched with NPCs. However, the role of NPCs in promoting pHGG tumor growth and invasion has not been explored.

In this project, we have demonstrated that NPC-conditioned medium significantly enhances cell proliferation and migration in patient-derived pHGG cells harboring various types of oncogenic mutations (e.g., H3.K27M and H3.G34R). Mechanistically, treatment of pHGG cells with NPC-conditioned medium significantly upregulates the expression of growth and proliferative markers (p-MTOR, p-FGF and FOS) alongside with neural stem cell markers (NESTIN and SOX2). These findings suggest that NPCs may contribute to tumor growth by activating the cancer stem cell population through secreted oncogenic factors, leading to systemic tumour growth and invasion. Taken together, we have shown for the first time NPCs play a direct oncogenic function in advancing pHGG tumour development.