Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve sheath tumours (MPNSTs).
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.
Maria
M
Demestre
Menderes Yusuf
MY
Terzi
Victor
V
Mautner
Peter
P
Vajkoczy
Andreas
A
Kurtz
Ana Luisa
AL
Piña
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D005136:Eye Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D009414:Nerve Growth Factors / Q000378:metabolism*; D009442:Neurilemmoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D015843:Serpins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor