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Neurofibrosarcoma‐derived Schwann cells overexpress platelet‐derived growth factor (PDGF) receptors and are induced to proliferate by PDGF BB

Neurofibromatosis type 1 (NF1) is characterized by the formation of neurofibromas, benign tumors of the peripheral nerve consisting essentially of Schwann cells, which can sometimes turn malignant to form neurofibrosarcomas. The mechanism of progression toward a malignant phenotype remains largely unknown. In this report, we show that platelet‐derived 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 (from a non‐NF1 patient) or for transformed rat Schwann cells. Levels of expression of both PDGF receptor α and β are significantly increased in the two neurofibrosarcoma‐derived cell lines compared to the non‐NF1 Schwann cell lines. The level of tyrosyl‐phosphorylated PDGF receptor β is strongly increased upon stimulation by PDGF BB. In comparison, only modest levels of tyrosyl‐phosphorylated PDGF receptor α are observed, upon stimulation by PDGF AA or PDGF BB. Accordingly, PDGF AA is only a weak mitogen for the neurofibrosarcoma‐derived cells by comparison to PDGF BB. These results indicate that the mitogenic effect of PDGF BB for the neurofibrosarcoma‐derived Schwann cell lines is primarily transduced by PDGF receptor β. Neu differentiation factor β, a potent mitogen for normal Schwann cells, was unable to stimulate proliferation of the transformed Schwann cell lines, due to a dramatic down‐regulation of the erbB3 receptor. Therefore, aberrant expression of growth factor receptors by Schwann cells, such as the PDGF receptors, could represent an important step in the process leading to Schwann cell hyperplasia in NF1. J. Cell. Physiol. 177:334–342, 1998. © 1998 Wiley‐Liss, Inc. The information in the article does not reflect government policy and no official endorsement should be inferred.