Invited Presentation 36th Lorne Cancer Conference 2024

Uncovering dynamic changes in Medulloblastoma associated vasculature in zebrafish. (#2)

Anne Karine Lagendijk 1 , E. Morris 1 , S. Daignault-Mill 1 , R. Ju 1 , J. da Silva 1 , A. Millar 1 , E. Tolson 1 , E. Gordon 1 , BJ. Wainwright 1 , S. Stehbens 1 , LA. Genovesi Genovesi 1
  1. Institute for Molecular Bioscience, St Lucia, QLD, Australia

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 differences 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 are. This gap in our knowledge is mainly due to the lack of models that allow long term live imaging.

Here we have established a xenograft approach to examine human MB tumour cells in zebrafish embryonal brains. We used this model to identify MB induced changes to associated vasculature. MB clusters co-opt with the vasculature and inflict a gradual decline of the vessels in the core. These compromised vessels also lack pericytes, suggesting that the BBB function is altered. Vessel decline is compensated by tumour angiogenesis and new vessels arise on the outside of the clusters. Currently work aims to determine the functionality of MB associated vessels, and test efficacy on systemic drugs.