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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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Main Authors: Roth, Patrick (Author) , Junker, Markus (Author) , Tritschler, Isabel (Author) , Mittelbronn, Michel (Author) , Dombrowski, Yvonne (Author) , Breit, Samuel N. (Author) , Tabatabai, Ghazaleh (Author) , Wick, Wolfgang (Author) , Weller, Michael (Author) , Wischhusen, Jörg (Author)
Format: Article (Journal)
Language:English
Published: July 28 2010
In: Clinical cancer research
Year: 2010, Volume: 16, Issue: 15, Pages: 3851-3859
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-10-0705
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1078-0432.CCR-10-0705
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Author Notes: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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Summary: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.
Item Description:Gesehen am 21.06.2023
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-10-0705

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