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Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumours (MPNSTs)

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Abstract

Neurofibromatosis type 1 (NF1) is an inherited genetic disease affecting 1 in 3,500 individuals. A prominent feature of NF1 is the formation of benign tumours of the peripheral nerve sheath (neurofibromas). However, these can become malignant and form highly metastatic malignant peripheral nerve sheath tumours (MPNST), which are usually fatal despite aggressive surgery, chemotherapy, and radiotherapy. Recent studies have shown that pigment epithelium-derived factor (PEDF) can induce differentiation and inhibit angiogenesis in several kinds of tumours. The present study was designed to determine the in vitro and in vivo effects of PEDF on MPNST angiogenesis and tumour growth. PEDF inhibited proliferation and augmented apoptosis in S462 MPNST cells after 48 h of treatment in culture. In xenografts of S462 MPNST cells in athymic nude mice, PEDF suppressed MPNST tumour burden, due mainly to inhibition of angiogenesis. These results demonstrate for the first time inhibitory effects of PEDF on the growth of human MPNST via induction of anti-angiogenesis and apoptosis. Our results suggest that PEDF could be a novel approach for future therapeutic purposes against MPNST.

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Acknowledgments

We would like to thank Professor C. Hagel for giving us advice on the MPNST tumours and allowing us to use their facilities (Department of Neuropathology, University Medical Center Hamburg Eppendorf, Hamburg, Germany). M. Spyra and Su Jin Park for technical assistance.

Conflict of interest

The authors declare no conflict of interests.

Funding

This work was supported by BCRT Flexible funds and Rahel Hirsch grants to ALP, by the US DoD Neurofibromatosis program (Grant W81XWH-05-1-0201) to AK, the Deutsche Krebshilfe (Grant 109713) to VM and the Bundesministerium für Bildung und Forschung (BMBF) (Grant 01GM0840) to AK and VM.

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Authors and Affiliations

  1. Department of Neurosurgery, Experimental Neurosurgery, Charité-Medical University, Chariteplatz 1/Virchowweg 21, Aschheim-Zondek-Haus 03-003, 10117, Berlin, Germany

    Menderes Yusuf Terzi, Peter Vajkoczy & Ana Luisa Piña

  2. Berlin-Brandenbug Center for Regenerative Therapies, Charité-Berlin Medical University, Augustenburger Platz 1, 13353, Berlin, Germany

    Andreas Kurtz & Ana Luisa Piña

  3. Department of Maxillofacial Surgery, University Hospital Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Maria Demestre & Victor Mautner

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  1. Maria Demestre
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  2. Menderes Yusuf Terzi
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  3. Victor Mautner
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  4. Peter Vajkoczy
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  5. Andreas Kurtz
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  6. Ana Luisa Piña
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Correspondence to Ana Luisa Piña.

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Maria Demestre and Menderes Yusuf Terzi equally contributed to this work.

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Demestre, M., Terzi, M.Y., Mautner, V. et al. Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumours (MPNSTs). J Neurooncol 115, 391–399 (2013). https://doi.org/10.1007/s11060-013-1252-x

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