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FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities

Oncogene volume 27, pages 4180–4190 (2008)Cite this article

Abstract

Fibroblast growth factor 5 (FGF5) is widely expressed in embryonic but scarcely in adult tissues. Here we report simultaneous overexpression of FGF5 and its predominant high-affinity receptor (FGFR1 IIIc) in astrocytic brain tumour specimens (N=49) and cell cultures (N=49). The levels of both ligand and receptor increased with enhanced malignancy in vivo and in vitro. Furthermore, secreted FGF5 protein was generally present in the supernatants of glioblastoma (GBM) cells. siRNA-mediated FGF5 downmodulation reduced moderately but significantly GBM cell proliferation while recombinant FGF5 (rFGF5) increased this parameter preferentially in cell lines with low endogenous expression levels. Apoptosis induction by prolonged serum starvation was significantly prevented by rFGF5. Moreover, tumour cell migration was distinctly stimulated by rFGF5 but attenuated by FGF5 siRNA. Blockade of FGFR1-mediated signals by pharmacological FGFR inhibitors or a dominant-negative FGFR1 IIIc protein inhibited GBM cell proliferation and/or induced apoptotic cell death. Moreover, rFGF5 and supernatants of highly FGF5-positive GBM cell lines specifically stimulated proliferation, migration and tube formation of human umbilical vein endothelial cells. In summary, we demonstrate for the first time that FGF5 contributes to the malignant progression of human astrocytic brain tumours by both autocrine and paracrine effects.

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Acknowledgements

We thank Ninon Taylor, Paracelsus Medical University Salzburg, for the dnFGFR1-IIIc adenoviral construct and for reading the paper. Moreover, we are thankful to Vera Bachinger, Christian Balcarek, Maria Eisenbauer and Heidelinde Cantonati for skilful technical assistance as well as Stoffl Mayer and Hedwig Sutterlüty for discussion of the data.This study was supported by Austrian Science Fund FWF, project number P17630-B12, P19920-B12 (to WB) and the Jubiläumsfonds des Bürgermeisters der Bundeshauptstadt Wien, project number 2569 (to CM).

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Authors and Affiliations

  1. Department of Medicine I, Institute of Cancer Research, Medical University Vienna, Vienna, Austria

    S Allerstorfer, G Sonvilla, H Fischer, C Gauglhofer, T Mohr, K Holzmann, B Grasl-Kraupp, B Marian, M Grusch, M Micksche & W Berger

  2. Department of Neurosurgery, Wagner Jauregg Hospital, Linz, Austria

    S Spiegl-Kreinecker, J Buchroithner & J Fischer

  3. Institute for Pathology and Bacteriology, Otto Wagner Hospital Baumgartner Höhe, Vienna, Austria

    U Setinek

  4. Department of Neurosurgery, Medical University Vienna, Vienna, Austria

    T Czech

  5. Department of Medicine I, Clinical Division of Oncology, Medical University Vienna, Vienna, Austria

    C Marosi

  6. Department of Internal Medicine, Wagner Jauregg Hospital, Linz, Austria

    J Pichler

  7. Institute of Pathology, Wagner Jauregg Hospital, Linz, Austria

    R Silye

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  1. S Allerstorfer
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Correspondence to W Berger.

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Allerstorfer, S., Sonvilla, G., Fischer, H. et al. FGF5 as an oncogenic factor in human glioblastoma multiforme: autocrine and paracrine activities. Oncogene 27, 4180–4190 (2008). https://doi.org/10.1038/onc.2008.61

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  • DOI: https://doi.org/10.1038/onc.2008.61

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