Article
Expression of GDF-15 in human glioma and its functions in glioblastoma cell lines
Expression und Funktion von GDF-15 in Glioblastomen und Glioblastom-Zelllinien
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Authors
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J. Strelau
- Department of Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN) University of Heidelberg
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C. Schmeer
- Department of Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN) University of Heidelberg
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H. Peterziel
- Department of Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN) University of Heidelberg
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C. Herold-Mende
- Molecular Biology Laboratory, Department of Neurosurgery, University of Heidelberg
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H. Steiner
- Molecular Biology Laboratory, Department of Neurosurgery, University of Heidelberg
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M. Weller
- Department of Neurology, University of Tübingen
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K. Unsicker
- Department of Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN) University of Heidelberg
| Published: | May 4, 2005 |
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Outline
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Objective
A divergent member of the TGF-beta superfamily that has been recently linked to the pathogenesis of cancer is growth differentiation factor-15 (GDF-15). Most recently, several reports have demonstrated functional links between GDF-15 and factors involved in tumorigenesis. Perhaps most excitingly, GDF-15 has been reported to exert proapoptotic and antitumorigenic functions on human colorectal, prostate, breast, and mammary cancer cells in vitro and on colon and glioblastoma tumors in vivo. Together, these findings strongly suggest a role of GDF-15 in tumor development and/or progression.
Methods
We used GDF-15 immunohistochemistry and real time PCR to analyse GDF-15 protein and mRNA expression. Proliferation- and invasion-assays were used for functional studies.
Results
We report here the expression of GDF-15 in human glioblastoma tissues, glioblastoma shortterm cultures, and glioblastoma cell lines. Our analyses reveal that GDF-15 stimulates proliferation of the cell lines LN-319, U87MG, A-172 and D-247, but has no effect on proliferation of LNT-229, LN-308, LN-428, LN-18 and U373MG cells. Neutralizing antibodies against GDF-15 attenuate the mitogenic activity of 8 cell lines. Furthermore, inhibition of GDF-15 decreases the invasiveness of LN-308, and U373MG cells, while LN-428 invasion is significantly increased.
Conclusions
In conclusion, we detected and quantified the expression of GDF-15 mRNA in human glioblastoma tissues, glioblastoma short-term cultures, and glioblastoma cell lines. In contrast to the documented proapoptotic and anti-tumorigenic activities of GDF-15 in several cancer cell lines, our data suggest that GDF-15 exerts a largely growth stimulating effect on glioblastoma cells. However, the underlying mechanisms leading to distinct functions of GDF-15 in tumors or tumor cell lines of different origin are largely unknown. Our findings together with other studies strongly suggest a role of GDF-15 in glioma tumor growth. Therefore, it is of particular interest to further explore GDF-15 dependent functions in tumorigenesis.
