MB-12: A NOVEL EX VIVO MODEL SYSTEM TO TARGET BRAIN INFILTRATION AND GROWTH OF MEDULLOBLASTOMA

Brain infiltration and growth of tumour cells in the cerebellum is a major cause of death in patients suffering from Medulloblastoma (MB). The consequent long distance spreading requires aggressive treatments that cause severe long-term morbidity. Till date, the processes of infiltration and metastatic dissemination of the MB tumour cells have remained obscure. Furthermore, total removal of the primary tumour is hampered at the microscopic level due to the insidious infiltration of the tumour cells into the surrounding brain tissue. Also, tumour recurrence occurs in one third of the patients with MB and might be caused by outgrowth of infiltrated, therapy-resistant tumour cells. This calls for an appropriate model system wherein living cerebellar tissue can be used as an ideal matrix for studying primary MB tumour cell invasion. Hence, we have established a novel organotypic cerebellar slice (OCS)-MB tumour co-culture system, in which MB tumour cell growth and infiltration into the matured slices can be monitored for at least 15 days. Using 3D invasion assays and a novel automated software tool for measuring dissemination, we have already identified HGF, EGF and bFGF as strong promoters of cell dissemination in established and primary MB cell lines. We are now using the OCS model as a pre-clinical platform to a) characterize local infiltration dynamics and morphological aspects within the tumour microenvironment, b) determine growth parameters of primary and secondary cell clusters and c) validate potential druggable therapy targets directed towards MB tumour cells using OCS culture for SHH and group 3 MB.