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Stimulation
Of Glioblastoma And Cerebral Microvascular Endothelial Cell Migration By
Tumor-Associated Growth Factors
Marc
A. Brockmann, Ulrike Ulbricht, Regina Fillbrandt, Manfred Westphal, and Katrin
Lamszus
Department
of Neurosurgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Objective.
Glioma cell migration is determined by a complex interplay between soluble
motogens and extracellular matrix components.
Several growth factors are thought to be involved in glioma cell migration;
however, little is known about their motogenic potency relative to one another.
Methods.
Using modified
Boyden chamber assays, we compared the chemotactic effects of SF/HGF, TGF-α,
-β1 and -β2,
EGF, FGF-1 and -2, IGF-1 and -2, PDGF-AA and -BB, VEGF, PTN, and MK in
concentrations ranging from 1 pM to 50 nM on three different human glioblastoma
cell lines.
Checkerboard analyses distinguished between chemotaxis and chemokinesis.
We further investigated the motogenic effects on human cerebral microvascular
endothelial cells (CMECs) and analyzed receptor expression profiles.
Results.
SF/HGF was the
most potent chemotactic factor for all three glioblastoma cell lines, inducing
up to 33-fold stimulation of migration.
TGF-α showed the
second strongest effect (up to 17-fold stimulation), and FGF-1 was also
chemotactic for all three glioblastoma cell lines analyzed (maximally 4-fold
effect).
EGF, FGF-2, IGF-1 and -2, TGF-β1 and -β2
were chemotactic for one or two of the cell lines (2- to 4-fold effects),
whereas PDGF-AA and -BB, VEGF, PTN, and MK had no effect.
In contrast, the most potent stimulators of CMEC migration were PDGF-AA (4-fold)
and -BB (6-fold).
Conclusion.
The expression
levels of SF/HGF and TGF-α,
as well as their respective receptors MET and EGFR, are known to correlate with
glioma malignancy grade.
The particularly strong motogenic effects of these two growth factors suggest
that they could be promising targets for an antimigratory component of glioma
therapy directed at soluble mediators, at least in comparison with the 12 other
factors that were analyzed.
Copyright
© 2003 by the Society for Neuro-Oncology
Source: http://ninetta.ingentaselect.com/vl=8274130/cl=50/nw=1/rpsv/cw/dup/15228517/previews/031003
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