Medulloblastoma is a paediatric brain tumour arising in the cerebellum. While current protocols are very effective at treating these tumours, they often results in debilitating and life-long impairment for patients. Worldwide collaborative efforts have aimed to characterise medulloblastoma tumours in greater molecular detail with the hope of identifying therapeutic targets. Our analysis of patient samples showed high STAT3 mRNA levels correlated with poorer prognosis and a lower probability of relapse-free survival than low STAT3 levels. On this basis we investigated the role of STAT3 in a mouse model of medulloblastoma.
Sonic Hedgehog (SHh) Medulloblastoma represents one of the most common forms of the disease and is characterised by excessive signalling through the SHh pathway. We used Ptch1+/LacZ transgenic mice to replicate a genetic lesion commonly seen in human disease. In this model 25% of mice develop medulloblastoma within 6 months. When we removed STAT3 from the originating cell of this disease, cerebellar granule precursors (CGPs), using a cell-type specific Cre-Lox system tumour survival increased suggesting a role for STAT3 in SHh medulloblastoma.
More detailed analysis of tumours arising in this model revealed higher expression of Glial Fabrilliary Acidic Protein, a marker of glial differentiation in tumours lacking STAT3 compared with controls. It is possible that in the absence of STAT3, cells within the tumour are driven to differentiate rather than proliferate resulting in reduced tumour incidence or progression.