Modelling Glioma Stem Cell-mediated Tumorigenesis Using Zebrafish PDX Systems

Abstract

Glioblastoma is an aggressive brain tumour associated with high post-therapy recurrence and very poor survival rates. One of the factors contributing to the aggressive nature of this disease is the level of heterogeneity seen at the phenotypic and genetic level. Glioma Stem Cells (GSCs) are stem-like cells within the tumour with the ability to self-renew and give rise to different types of cells within the tumour, hence giving rise to the heterogeneity found in glioblastoma. GSCs are often implicated in the resistance of glioma to standard of care radiation and chemotherapy. The physical niche within a tumour mass supports stemness and aggressive characteristics of GSCs, hence, experimental systems providing a relevant tumour microenvironment are critical for adequate assessment of molecular mechanisms regulating GSC populations. Although, mouse models are a staple of an in vivo experimental design, they are neither time-nor cost-efficient. Danio rerio (zebrafish) patient-derived xenografts (PDXs) overcome several of the obstacles of the mammalian systems. Zebrafish constitute a high throughput, easily reproducible experimental platform allowing for life relevant investigation into the aggressiveness of GSC populations. This chapter describes methods required for generation of zebrafish PDXs to study aspects of GSC-mediated tumorigenesis and interactions with the tumour microenvironment. Consistency between labs for these experiments is required to move the discovery of effective treatments for glioblastoma moving forward.