NEUROFIBROSARCOMA-DERIVED SCHWANN-CELLS OVEREXPRESS PLATELET-DERIVED GROWTH-FACTOR (PDGF) RECEPTORS AND ARE INDUCED TO PROLIFERATE BY PDGF BE

Neurofibromatosis type 1 (NF1) is characterized by the formation of ne urofibromas, benign tumors of the peripheral nerve consisting essentia lly of Schwann cells, which can sometimes turn malignant to form neuro fibrosarcomas. The mechanism of progression toward a malignant phenoty pe remains largely unknown. In this report, we show that platelet-deri ved growth factor (PDGF) BB, and to a lesser extent fibroblast growth factor 2, are mitogenic for two neurofibrosarcoma-derived Schwann cell lines, but not for a Schwann cell line derived from a schwannoma (fro m a non-NF1 patient) or for transformed rat Schwann cells. Levels of e xpression of both PDGF receptor alpha and beta are significantly incre ased in the two neurofibrosarcoma-derived cell lines compared to the n on-NF1 Schwann cell lines. The level of tyrosyl-phosphorylated PDGF re ceptor beta is strongly increased upon stimulation by PDGF BE. In comp arison, only modest levels of tyrosyl-phosphorylated PDGF receptor alp ha are observed, upon stimulation by PDGF AA or PDGF BE. Accordingly, PDGF AA is only a weak mitogen for the neurofibrosarcoma-derived cells by comparison to PDGF BB. These results indicate that the mitogenic e ffect of PDGF BE for the neurofibrosarcoma-derived Schwann cell lines is primarily transduced by PDGF receptor beta. Neu differentiation fac tor beta, a potent mitogen for normal Schwann cells, was unable to sti mulate proliferation of the transformed Schwann cell lines, due to a d ramatic downregulation of the erbB3 receptor. Therefore, aberrant expr ession of growth factor receptors by Schwann cells, such as the PDGF r eceptors, could represent an important step in the process leading to Schwann cell hyperplasia in NF1. J. Cell. Physiol. 177:334-342, 1998. (C) 1998 Wiley-Liss, Inc.