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Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic <jats:italic>MYC<\/jats:italic> amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA) and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration\/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri-\/sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in <jats:italic>MYC<\/jats:italic> amplified medulloblastoma prioritized IGF1R inhibitors. 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C.K. has also been a paid consultant to the NCI\/CTEP Pediatric Preclinical Testing Program (PPTP). The remaining authors have no other conflicts to declare related to these studies except that a first-degree relative of a BMS scientist was in the past an employee in our laboratory.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"27012"}}