Codo, Paula and Weller, Michael and Kaulich, Kerstin and Schraivogel, Daniel and Silginer, Manuela and Reifenberger, Guido and Meister, Gunter and Roth, Patrick (2016) Control of glioma cell migration and invasiveness by GDF-15. ONCOTARGET, 7 (7). pp. 7732-7746. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-beta family of proteins. GDF-15 levels are increased in the blood and cerebrospinal fluid of glioblastoma patients. Using a TCGA database interrogation, we demonstrate that high GDF-15 expression levels are associated with poor survival of glioblastoma patients. To elucidate the role of GDF-15 in glioblastoma in detail, we confirmed that glioma cells express GDF-15 mRNA and protein in vitro. To allow for a detailed functional characterization, GDF-15 expression was silenced using RNA interference in LNT-229 and LN-308 glioma cells. Depletion of GDF-15 had no effect on cell viability. In contrast, GDF-15-deficient cells displayed reduced migration and invasion, in the absence of changes in Smad2 or Smad1/5/8 phosphorylation. Conversely, exogenous GDF-15 stimulated migration and invasiveness. Large-scale expression profiling revealed that GDF-15 gene silencing resulted in minor changes in the miRNA profile whereas several genes, including members of the plasminogen activator/inhibitor complex, were deregulated at the mRNA level. One of the newly identified genes induced by GDF-15 gene silencing was the serpin peptidase inhibitor, clade E nexin group 1 (serpine1) which is induced by TGF-beta and known to inhibit migration and invasiveness. However, serpine1 down-regulation alone did not mediate GDF-15-induced promotion of migration and invasiveness. Our findings highlight the complex contributions of GDF-15 to the invasive phenotype of glioma cells and suggest anti-GDF-15 approaches as a promising therapeutic strategy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MACROPHAGE INHIBITORY CYTOKINE-1; GROWTH-FACTOR-BETA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; TGF-BETA; GENE NAG-1/GDF15; IMMUNE ESCAPE; CANCER CELLS; GLIOBLASTOMA; MIC-1/GDF15; MIC-1; GDF-15; glioblastoma; invasion; TCGA; serpine1 |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie I > Prof. Dr. Gunter Meister |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2019 09:10 |
| Last Modified: | 12 Mar 2019 09:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2399 |
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