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

Cancers

Benjamin Neuditschko¹  Christopher Gerner¹  Andrea Bileck¹  Laura Niederstaetter¹  Johannes Gojo²  Andreas Peyrl²  Bernd Reichl³  Wolfgang Buchberger³  Thomas Boegl³ 

[1]Department of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, Austria

[2]Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

[3]Institute of Analytical Chemistry, Johannes Kepler University, Altenberger Strasse 69, 4040 Linz, Austria

关键词: cerebrospinal fluid;    oxylipins;    hypoxia;    lipidomics;    mass spectrometry;    medulloblastoma;   

DOI  :  10.3390/cancers12061350

来源: DOAJ

【 摘 要 】

Molecular classification of medulloblastoma (MB) is well-established and reflects the cell origin and biological properties of tumor cells. However, limited data is available regarding the MB tumor microenvironment. Here, we present a mass spectrometry-based multi-omics pilot 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 characteristic tumor markers, including FSTL5, ART3, and FMOD, 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 hypoxic conditions in the CSF of MB patients. This notion was independently supported by metabolomics, demonstrating the up-regulation of tryptophan, methionine, serine and lysine, which have all been described to be induced upon hypoxia in CSF. While cyclooxygenase products were hardly detectable, the epoxygenase product and beta-oxidation promoting lipid hormone 12,13-DiHOME was found to be strongly up-regulated. Taken together, the data suggest a vicious cycle driven by autophagy, the formation of 12,13-DiHOME and increased beta-oxidation, thus promoting a metabolic shift supporting the formation of drug resistance and stem cell properties of MB cells. In conclusion, the different omics-techniques clearly synergized and mutually supported a novel model for a specific pathomechanism.

【 授权许可】

Unknown