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Stimulation Of Glioblastoma And Cerebral Microvascular Endothelial Cell Migration By Tumor-Associated Growth Factors

Posted on: 11/17/2003

Society for Neuro-Oncology Eighth Annual Meeting. Keystone, Colorado. November 13–16, 2003. Abstract No. AN-04. Neuro-Oncology, Volume 5, Issue 4, October 2003

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-á, -â1 and -â2, 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-á 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-â1 and -â2 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-á, 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


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