Medulloblastoma (MB), the most common malignant pediatric
brain tumor, has high propensity to metastasize. Currently, the standard treatment for MB patients includes
radiation therapy administered to the entire brain and spine for the purpose of treating or preventing against
metastasis. Due to this aggressive treatment, the majority of long-term survivors will be left with permanent and debilitating neurocognitive impairment, for the 30-40% patients that fail to respond to treatment, all will relapse with terminal metastatic disease. An understanding of the underlying biology that drives MB
metastasis is lacking, and is critically needed in order to develop targeted
therapeutics for its prevention. To examine the metastatic biology of sonic hedgehog (SHH) MB, the human MB subgroup with the worst clinical outcome in children, we first generated a robust SmoA1-Math-GFP mouse model that reliably reproduces human SHH MB whereby
metastases can be visualized under fluorescence microscopy. Lipidome alterations associated with
metastasis were then investigated by applying ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) under positive ionization mode to primary
tumor samples collected from mice without (n = 18) and with (n = 7)
metastasis. Thirty-four discriminant
lipids associated with SHH MB
metastasis were successfully annotated, including
ceramides (Cers),
sphingomyelins (SMs),
triacylglycerols (TGs),
diacylglycerols (DGs),
phosphatidylcholines (PCs), and
phosphatidic acids (PAs). This study provides deeper insights into dysregulations of lipid metabolism associated with SHH MB metastatic progression, and thus serves as a guide toward novel targeted
therapies.