Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid
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...
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MDPI AG
2020-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1350 |
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| author | Bernd Reichl Laura Niederstaetter Thomas Boegl Benjamin Neuditschko Andrea Bileck Johannes Gojo Wolfgang Buchberger Andreas Peyrl Christopher Gerner |
| author_facet | Bernd Reichl Laura Niederstaetter Thomas Boegl Benjamin Neuditschko Andrea Bileck Johannes Gojo Wolfgang Buchberger Andreas Peyrl Christopher Gerner |
| author_sort | Bernd Reichl |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:36:01Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:36:01Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c82b47b3ca3245409eda4fde3121865e2023-11-20T01:44:44ZengMDPI AGCancers2072-66942020-05-01126135010.3390/cancers12061350Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal FluidBernd Reichl0Laura Niederstaetter1Thomas Boegl2Benjamin Neuditschko3Andrea Bileck4Johannes Gojo5Wolfgang Buchberger6Andreas Peyrl7Christopher Gerner8Institute of Analytical Chemistry, Johannes Kepler University, Altenberger Strasse 69, 4040 Linz, AustriaDepartment of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaInstitute of Analytical Chemistry, Johannes Kepler University, Altenberger Strasse 69, 4040 Linz, AustriaDepartment of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaDepartment of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaDepartment of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaInstitute of Analytical Chemistry, Johannes Kepler University, Altenberger Strasse 69, 4040 Linz, AustriaDepartment of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Analytical Chemistry, University of Vienna, Waehringer Straße 38, 1090 Vienna, AustriaMolecular 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.https://www.mdpi.com/2072-6694/12/6/1350cerebrospinal fluidoxylipinshypoxialipidomicsmass spectrometrymedulloblastoma |
| spellingShingle | Bernd Reichl Laura Niederstaetter Thomas Boegl Benjamin Neuditschko Andrea Bileck Johannes Gojo Wolfgang Buchberger Andreas Peyrl Christopher Gerner Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid Cancers cerebrospinal fluid oxylipins hypoxia lipidomics mass spectrometry medulloblastoma |
| title | Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid |
| title_full | Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid |
| title_fullStr | Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid |
| title_full_unstemmed | Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid |
| title_short | Determination of a Tumor-Promoting Microenvironment in Recurrent Medulloblastoma: A Multi-Omics Study of Cerebrospinal Fluid |
| title_sort | determination of a tumor promoting microenvironment in recurrent medulloblastoma a multi omics study of cerebrospinal fluid |
| topic | cerebrospinal fluid oxylipins hypoxia lipidomics mass spectrometry medulloblastoma |
| url | https://www.mdpi.com/2072-6694/12/6/1350 |
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