Pigment epithelium-derived factor (PEDF) is a multifunctional protein with known anti-angiogenic and trophic properties, capable of promoting the survival and growth of Schwann cells (SC). Normal rat SCs and ganglioneuroma-derived human SCs secrete PEDF. The ability of normal SC to secrete a number of trophic factors is controlled by axonal contact. Normal human Schwann cells (HSC) and malignant peripheral nerve sheath tumors (MPNST) cell lines synthesize and secrete PEDF as determined by reverse transcription PCR analysis for PEDF mRNA, immunocytochemistry, and Western blot analysis for PEDF protein. Two MPNST cell lines secreted higher levels of PEDF than did HSC. A 90.3% decrease in PEDF mRNA and a 29.3% decrease in secreted PEDF were observed after treatment of HSC with axolemma-enriched fraction (AEF, 100 microg/ml), a neuronal membrane fraction of the axonal plasma membrane used with cultured SC to mimic axonal contact in vitro. PEDF levels remained unchanged, however, in MPNST-derived SC conditioned media under the same treatment paradigm. These results suggest that MPNST SC lose the ability to downregulate PEDF upon axonal contact, which is characteristic of HSC. The elevated PEDF levels expressed by MPNST cell lines may serve to promote their proliferation and survival.
Copyright 2004 Wiley-Liss, Inc.