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Functional significance of vascular
endothelial growth factor receptor expression on human glioma cells
Mentlein R, Forstreuter F, Mehdorn HM, Held-Feindt J
Department of Anatomy, University of Kiel, Kiel, Germany.
rment@anat.uni-kiel.de
Vascular endothelial growth factor (VEGF) is one of the most important
angiogenesis factors.
In many tumors, VEGF plays a pivotal role for their vascularization and is
necessary to supply the malignant tissue with oxygen and nutrients.
However, VEGF receptors (VEGFR) have recently been detected also on some tumor
cells, and autocrine mitogenic effects of VEGF have been suspected.
Since glioma cells are known to produce large amounts of VEGF, we investigated
VEGFR-expression and effects of VEGF on glioma cells.
The three glioma cell lines and eight glioma cells cultivated from WHO grade IV
gliomas investigated strongly expressed VEGF121 and VEGF165, but weakly either
VEGFR-1 or -2, sometimes for both, as evidenced by reverse
transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry.
Quantitative RT-PCR revealed a 1000- to 50-fold lower expression of VEGFR than
in cultivated human umbilical vein endothelial cells.
In two glioma cell lines analyzed, VEGF induced a weak tyrosine phosphorylation
of the VEGFR, but downstream signal transduction effects on the
mitogen-activated protein kinases p42/p44 or transcription factors like AP-1 or
NFKB were within the background of the methods.
In accordance, VEGF or the VEGFR agonists VEGF-D or placenta growth factor
(P1GF) did not produce significant effects on glioma cell proliferation or VEGF
production.
We conclude that despite a low expression of VEGFR in some glioma cells
functional effects are low and autocrine growth stimulatory effects within a
glioma are minor.
PMID: 15072443 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15072443
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