title: Migration induced by epidermal and hepatocyte growth factors in oral squamous carcinoma cells in vitro: role of MEK/ERK, p38 and PI-3 kinase/Akt.
abstract: BACKGROUND
  Cell migration is a necessary part of malignant invasiveness. Oral squamous cell carcinomas (OSCC) have a great tendency for local invasive growth. We have investigated signalling pathways involved in cell migration induced by epidermal growth factor (EGF) and hepatocyte growth factor (HGF) in OSCC cells and examined the effects of various experimental and clinically approved anti-tumour signal inhibitors on the migratory activity.
  
  
  METHODS
  Migration was studied in three human OSCC cell lines, using a scratch wound assay in vitro and time-lapse cinematography. Specific phosphorylation of signalling proteins was assessed by Western blotting.
  
  
  RESULTS
  In the E10 cell line, EGF and HGF induced phosphorylation of EGF receptor (EGFR) and Met, respectively, phosphorylation of ERK1/2, p38 and Akt, and dose-dependent activation of cell migration. Addition of the EGFR-specific inhibitors cetuximab (antibody) or gefitinib (tyrosine kinase blocker) abolished cell migration elicited by EGF. Similarly, a Met kinase inhibitor (SU11274) blocked HGF-induced cell migration. Furthermore, when three cell lines were treated with blockers of the MEK/ERK, p38 or the PI-3 kinase/Akt pathways, the migratory response to both EGF and HGF was inhibited, but to varying degrees. Notably, in E10 and D12 cells, HGF-induced migration was particularly sensitive to PI-3 K-inhibition, while in C12 cells, both HGF- and EGF-induced migration were highly sensitive to p38-blockade.
  
  
  CONCLUSIONS
  The results demonstrate that the MEK/ERK, p38 and PI-3 kinase pathways are all involved in mediating the increased migration in OSCC cell lines induced by EGF and HGF, but their relative importance and the effects of specific signal inhibitors differ.
authors.affiliation: Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway. i.j.brusevold@medisin.uio.no
authors.forename: Ingvild J
authors.initials: IJ
authors.lastname: Brusevold
authors.forename: Monica
authors.initials: M
authors.lastname: Aasrum
authors.forename: Magne
authors.initials: M
authors.lastname: Bryne
authors.forename: Thoralf
authors.initials: T
authors.lastname: Christoffersen
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D058539:Phosphatidylinositol 3-Kinase