GDF-15 contributes to proliferation and immune escape of malignant gliomas
Purpose: Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family. GDF-15 is necessary for the maintenance of pregnancy but has also been linked to other physiologic and pathologic conditions.Experimental Design: The expression of GDF-15 in glioma cell...
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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
July 28 2010
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| In: |
Clinical cancer research
Year: 2010, Jahrgang: 16, Heft: 15, Pages: 3851-3859 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-10-0705 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-10-0705
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| Verfasserangaben: | Patrick Roth, Markus Junker, Isabel Tritschler, Michel Mittelbronn, Yvonne Dombrowski, Samuel N. Breit, Ghazaleh Tabatabai, Wolfgang Wick, Michael Weller, and Jörg Wischhusen |
MARC
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| 245 | 1 | 0 | |a GDF-15 contributes to proliferation and immune escape of malignant gliomas |c Patrick Roth, Markus Junker, Isabel Tritschler, Michel Mittelbronn, Yvonne Dombrowski, Samuel N. Breit, Ghazaleh Tabatabai, Wolfgang Wick, Michael Weller, and Jörg Wischhusen |
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| 520 | |a Purpose: Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family. GDF-15 is necessary for the maintenance of pregnancy but has also been linked to other physiologic and pathologic conditions.Experimental Design: The expression of GDF-15 in glioma cell lines was assessed by quantitative reverse transcriptase-PCR and immunoblot. GDF-15 levels in situ and in the peripheral blood of glioma patients were examined by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The effects of short hairpin RNA-mediated GDF-15 inhibition on proliferation and immunogenicity of SMA-560 glioma cells were investigated by [methyl-3H]thymidine incorporation and immune-mediated target cell lysis. The impact of GDF-15 on glioma growth in vivo was assessed in syngeneic mice.Results: GDF-15 is expressed by gliomas of different WHO grades as assessed by immunohistochemistry. The high expression of GDF-15 in tumor tissue translates into elevated GDF-15 serum levels in glioblastoma patients compared with healthy controls. GDF-15 mRNA and protein are also detectable in human and mouse glioma cells in vitro. Silencing of GDF-15 by RNA interference reduces the proliferation of malignant glioma cells. Immunologically, the depletion of glioma-derived GDF-15 enhances the susceptibility of mouse glioma cells towards syngeneic natural killer cells and splenocytes. This results in a reduced in vivo tumorigenicity and increased T-cell infiltration of GDF-15-deficient glioma cells in syngeneic mice.Conclusions: Although previous studies focusing on ectopic overexpression of GDF-15 have proposed unclear or antitumorigenic effects of GDF-15 in glioma cells, we here show that GDF-15 at endogenous levels contributes to proliferation and immune escape of malignant gliomas in an immunocompetent host. Clin Cancer Res; 16(15); 3851-9. ©2010 AACR. | ||
| 700 | 1 | |a Junker, Markus |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tritschler, Isabel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mittelbronn, Michel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dombrowski, Yvonne |e VerfasserIn |4 aut | |
| 700 | 1 | |a Breit, Samuel N. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tabatabai, Ghazaleh |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wick, Wolfgang |d 1970- |e VerfasserIn |0 (DE-588)120297736 |0 (DE-627)080586929 |0 (DE-576)186221320 |4 aut | |
| 700 | 1 | |a Weller, Michael |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wischhusen, Jörg |e VerfasserIn |4 aut | |
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