Wnt signaling promotes phenotypic reprogramming of glioblastoma-derived cells in the zebrafish brain microenvironment

The definition of tumour niche signals involved in brain tumours stem cell maintenance is crucial to understand the leading cause of glioblastoma onset, progression and relapse. We have injected primary glioblastoma-derived cells into the brain peri-ventricular zone of zebrafish larvae, nowadays considered to be a suitable animal model for orthotopic xeno-transplantation, and evaluated the phenotypic reprogramming potency of the zebrafish brain microenvironment. Glioblastoma-derived cells infiltrated the zebrafish brain tissue, undergoing a progressive loss of stemness and proliferation markers and acquiring a neuronal, differentiated phenotype. In this model, we observed that phenotypic reprogramming of glioblastoma cells could be majorly attributed to the activation of Wnt pathway by endogenous zebrafish Wnt ligands. The possible role of Notch signaling in mediating this activity will be presented and discussed.