title: Glioblastoma and cerebral microvascular endothelial cell migration in response to tumor-associated growth factors.
abstract: 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 scatter factor/hepatocyte growth factor (SF/HGF), transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, epidermal growth factor (EGF), fibroblast growth factor (FGF)-1, FGF-2, insulin-like growth factor (IGF)-1, IGF-2, platelet-derived growth factor (PDGF)-AA, PDGF-BB, vascular endothelial growth factor (VEGF), pleiotrophin (PTN), and midkine (MK) in concentrations ranging from 1 pmol/L to 50 nmol/L 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 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-alpha showed the second strongest effect (up to 17-fold stimulation), and FGF-1 was also chemotactic for all three glioblastoma cell lines analyzed (maximal 4-fold effect). EGF, FGF-2, IGF-1, IGF-2, TGF-beta1, and TGF-beta2 were chemotactic for one or two of the cell lines (2- to 4-fold effects), whereas PDGF-AA, PDGF-BB, VEGF, PTN, and MK had no effect. In contrast, the most potent stimulators of cerebral microvascular endothelial cell migration were PDGF-AA (4-fold) and PDGF-BB (6-fold).
  
  
  CONCLUSIONS
  The expression levels of SF/HGF and TGF-alpha 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, at least in comparison with the 12 other factors that were analyzed.
authors.affiliation: Hans-Dietrich Herrmann Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. lamszus@uke.uni-hamburg.de
authors.forename: Marc-Alexander
authors.initials: MA
authors.lastname: Brockmann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ulbricht
authors.forename: Katrin
authors.initials: K
authors.lastname: Grüner
authors.forename: Regina
authors.initials: R
authors.lastname: Fillbrandt
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Katrin
authors.initials: K
authors.lastname: Lamszus
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000503:physiopathology*; D002352:Carrier Proteins / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D002630:Chemotactic Factors / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005909:Glioblastoma / Q000503:physiopathology*; D006133:Growth Substances / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D000078792:Midkine; D008934:Mitogens / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013002:Somatomedins / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D002352:Carrier Proteins; D002630:Chemotactic Factors; D016207:Cytokines; D006133:Growth Substances; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D013002:Somatomedins; C066845:pleiotrophin; D000078792:Midkine; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D015291:Transforming Growth Factors