Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumours (MPNSTs)
- PDF / 755,882 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 41 Downloads / 189 Views
LABORATORY INVESTIGATION
Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumours (MPNSTs) Maria Demestre • Menderes Yusuf Terzi • Victor Mautner • Peter Vajkoczy • Andreas Kurtz Ana Luisa Pin˜a
•
Received: 2 March 2013 / Accepted: 17 September 2013 / Published online: 28 September 2013 Ó Springer Science+Business Media New York 2013
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
Maria Demestre and Menderes Yusuf Terzi equally contributed to this work. M. Demestre V. Mautner Department of Maxillofacial Surgery, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany M. Y. Terzi P. Vajkoczy A. L. Pin˜a (&) Department of Neurosurgery, Experimental Neurosurgery, Charite´-Medical University, Chariteplatz 1/Virchowweg 21, Aschheim-Zondek-Haus 03-003, 10117 Berlin, Germany e-mail: [email protected] A. Kurtz A. L. Pin˜a Berlin-Brandenbug Center for Regenerative Therapies, Charite´-Berlin Medical University, Augustenburger Platz 1, 13353 Berlin, Germany
anti-angiogenesis and apoptosis. Our results suggest that PEDF could be a novel approach for future therapeutic purposes against MPNST. Keywords PEDF MPNST Tumor growth Angiogenesis Anti-angiogenesis NF1
Introduction Neurofibromatosis type 1 (NF1) is a rare inherited disease affecting 1 in 3,500 individuals. A prominent feature of NF1 is the formation of benign plexiform neurofibromas (PNFs), which frequently transform into highly metastatic malignant peripheral nerve sheath tumours (MPNSTs) [22]. MPNSTs are the most common malignancy in NF1 and are usually fatal despite aggressive surgery, chemotherapy, and radiotherapy [22]. NF1-derived tumours are very rich in blood vessels [3] and the growth of NF1 tumours is known to be angiogenesis dependent [36]. It has been demonstrated that Schwann cells (SCs) are the tumour cells in NF1-associated benign neurofibromas and PNFs [21, 28]. While the exact origin of MPNSTs remains unclear, SCs are thought to be the neoplastic cells in MPNST, since PNFs are the
Data Loading...
