Determination of a tumor-promoting microenvironment in recurrent medulloblastoma: a multi-omics study of cerebrospinal fluid

ABSTRACT: Molecular characterization of medulloblastoma (MB) cell origin and properties is the basis for a well-defined classification system. However, limited data is available regarding the MB tumor microenvironment. Here we present a mass spectrometry-based multi-omics study of cerebrospinal fluid (CSF) from recurrent MB patients. A group of age-matched patients without a neoplastic disease was used as control cohort. Proteome profiling identified several characteristic tumor markers and revealed a strong prevalence of anti-inflammatory and tumor-promoting proteins characteristic for alternatively polarized myeloid cells in MB samples. The up-regulation of ADAMTS1, GAP43 and GPR37 indicated hypoxia in CSF of MB patients. This notion was independently supported by metabolomics, demonstrating up-regulation of tryptophan, methionine, serine and lysine, all of which have been described to be induced upon hypoxia in CSF. The beta-oxidation promoting lipid hormone 12,13-DiHOME was found strongly upregulated, potentially promoting a metabolic shift supporting drug resistance and stem cell properties of MB cells.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

DISEASE(S): Medulloblastoma

SUBMITTER: Christopher Gerner  

LAB HEAD: Christopher Gerner

PROVIDER: PXD018226 | Pride | 2020-06-01

REPOSITORIES: Pride