Publication: Platelet-Derived Growth Factor PDGF in primary brain tumours of neuroglial origin
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Date
1998
Authors
Smits, A. ; Funa, K.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
It has become clear that disruptions in the
genome of somatic cells play a causative role in tumour
development. We know that the ultimate formation of a
malignancy is the result of a multistep process in which
the functional loss andlor the altered or increased
expression of genes play important roles. One such
family of genes are the oncogenes, encoding protein
products with mainly growth stimulating effects.
Platelet-derived growth factor (PDGF) belongs to the
family of oncogenes. It is likely that PDGF plays an
essential role in the development of at least a subgroup
of malignant astrocytic tumours that do not contain
amplification of the EGF-receptor. The expression of
PDGF a-receptors is related to tumour progression in
these tumours, and some of the most malignant tumours
were shown to contain amplification of the PDGF areceptor.
It is also clear now from several experimental
studies that PDGF can drive the transformed phenotype,
and that PDGF antagonists, by blocking the PDGF
autocrine pathway revert the transformed phenotype of
certain tumour cells. Because of the findings that
receptor protein tyrosine kinases such as the EGF- and
the PDGF-receptor play a crucial role in the development
of gliomas, it is possible that inhibitors of the
phosphorylation of the protein tyrosine kinases will be
future candidates for glioma therapy. They might be able
to at least delay the development of a fully malignant
glioma. The role of PDGF in other tumours of neuroglial
origin in the central nervous system has not been studied
as extensively as its role in gliomas. Recent data suggest
that also for the primitive neuroectodermal tumours
overexpression of the PDGF a-receptor is related to
malignancy of the tumours. For other tumours, such as
neuroblastomas, PDGF exerts a differentiating rather
than a mitogenic function and is an important survival
factor. Further studies are needed to elucidate the role of
PDGF in these non-glial primary brain tumours.
Moreover, for a complete understanding of the role of
PDGF in malignancies of the CNS, it is important to
explore its function in the development of the normal
Offprint requests to: Dr. Anja Smits, Department of Neurology,
University Hospital Uppsala, S-751 85 Uppsala, Sweden
CNS further.
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