MBRS-43. MODELLING MEDULLOBLASTOMA INVASION AND CHEMORESISTANCE IN A 3D HYALURONAN HYDROGEL SYSTEM

Abstract

Medulloblastoma (MB) is the most common malignant paediatric brain tumour. High rates of metastasis and chemoresistance demand new, subgroup specific therapy approaches. The development of reliable and realistic model systems will allow us to investigate and compare processes such as invasion and chemoresistance as well as the underlying pathways. We are using a hyaluronan (HA) based hydrogel system that mimics the cerebellum and can be further modified to higher complexity using additional extracellular matrix components. The four different molecular MB subgroups are characterized by different metastatic patterns and aspects of these are reflected by our model system. Group 3 cell lines demonstrate laminar coating whereas group 4 and SHH cells show mainly nodular growth. Using an isogenic and recurrent metastatic group 4 cell line pair we have been able to demonstrate that the cell lines grow and establish small tumour masses with diameters of more than 1mm when they are embedded in the HA hydrogel for several months. Those tumour cell masses attract single surrounding cells as well as smaller cell clusters. Interestingly, the recurrent cell line grows more aggressively in 3D and tumour cells are more resistant to chemotherapeutic reagents in the gel model. Our results highlight the potential of 3D model systems for MB clinical target evaluations. Further characterization of MB cell lines embedded in the hydrogel model will provide deeper insight into potential subgroup specific molecular targets in order to better treat and potentially prevent metastasis and chemoresistance.