A. Badache et Gh. Devries, NEUROFIBROSARCOMA-DERIVED SCHWANN-CELLS OVEREXPRESS PLATELET-DERIVED GROWTH-FACTOR (PDGF) RECEPTORS AND ARE INDUCED TO PROLIFERATE BY PDGF BE, Journal of cellular physiology, 177(2), 1998, pp. 334-342
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.