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Platelet-Derived Growth Factor (PDGF) in primary brain tumours of
neuroglial origin
A. Smits1 and K. Funa2
1Department of Neurology, University Hospital Uppsala,
Uppsala, Sweden and 2Ludwig Institute for Cancer Research, Biomedical Center,
Uppsala, Sweden (Present address: Institute of Anatomy and Cell Biology,
University of Gothenburg, Sweden)
Offprint requests to: Dr. Anja
Smits, Department of Neurology, University Hospital Uppsala, S-751 85 Uppsala,
Sweden
Summary. 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 and/or
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 a-receptor. 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
develop-ment 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 CNS further. Histol Histopathol 13, 511-520
(1998)
Key words: PDGF, PDGF-receptors,
Central nervous system, Brain tumours, Tumour progression, Gliomas
DOI: 10.14670/HH-13.511
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