Medulloblastoma (MB) is an embryonal-derived lesion arising in the cerebellum, contributing to 20% of all childhood brain tumours and 63% of all intracranial embryonal tumours. Current treatment options include surgical resection and chemotherapy, used in conjunction with radiation. While these treatments have significantly improved survival rates, the side effects of therapy such as neurological and neurocognitive impairments, can be detrimental to survivors’ quality of life. Furthermore, relapse occurs in 30% of patients and is fatal due to lack of effective treatments for relapsed tumours.
We hypothesize that the blood brain barrier (BBB) might be a major cause of ineffective treatments. Recent studies have identified that the BBB in the context of MB is highly heterogenous with variabilities in BBB cellular composition and integrity between MB sub-types and within single tumours. It remains unclear however, how these differences emerge and what the primary vascular defects since long term live imaging is extremely challenging in current gold-standard MB mouse models.
Here we have established a xenograft approach to examine human MB tumour cells in the zebrafish brain. We aim to use this model, in combination with transgenic zebrafish MB models, to identify characteristic changes of MB associated vasculature and how these impact on BBB functionality. Preliminary work has identified that MB tumour cells of the Group 3 subgroup are viable in the zebrafish brain and associate closely with blood vessels. This interaction further inflicts local changes in vessel network formation. By utilising our large range of transgenic zebrafish lines, we will continue to investigate how MB cells interact and alter distinctive BBB cell types, including endothelial cells, pericytes and astrocytes.