Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid.

作者: Bernd Reichl , Laura Niederstaetter , Thomas Boegl , Benjamin Neuditschko , Andrea Bileck

DOI: 10.3390/CANCERS12061350

关键词: Tumor microenvironmentProteomicsMedulloblastomaCancer researchAutophagyCerebrospinal fluidStem cellCellChemistryRecurrent Medulloblastoma

摘要: Molecular classification of medulloblastoma (MB) is well-established and reflects the cell origin biological properties tumor cells. However, limited data available regarding MB microenvironment. Here, we present a mass spectrometry-based multi-omics pilot study cerebrospinal fluid (CSF) from recurrent patients. A group age-matched patients without neoplastic disease was used as control cohort. Proteome profiling identified characteristic markers, including FSTL5, ART3, FMOD, revealed strong prevalence anti-inflammatory tumor-promoting proteins for alternatively polarized myeloid cells in samples. The up-regulation ADAMTS1, GAP43 GPR37 indicated hypoxic conditions CSF This notion independently supported by metabolomics, demonstrating tryptophan, methionine, serine lysine, which have all been described to be induced upon hypoxia CSF. While cyclooxygenase products were hardly detectable, epoxygenase product beta-oxidation promoting lipid hormone 12,13-DiHOME found strongly up-regulated. Taken together, suggest vicious cycle driven autophagy, formation increased beta-oxidation, thus metabolic shift supporting drug resistance stem In conclusion, different omics-techniques clearly synergized mutually novel model specific pathomechanism.

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