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

Abstract:

: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 alpha and beta 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 beta is strongly increased upon stimulation by PDGF BB. In comparison, only modest levels of tyrosyl-phosphorylated PDGF receptor alpha 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 beta. Neu differentiation factor beta, 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.

journal_name

J Cell Physiol

authors

Badache A,De Vries GH

doi

10.1002/(SICI)1097-4652(199811)177:2<334::AID-JCP1

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

334-42

issue

2

eissn

0021-9541

issn

1097-4652

pii

10.1002/(SICI)1097-4652(199811)177:2<334::AID-JCP1

journal_volume

177

pub_type

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