title: Integrin-based meningioma cell migration is promoted by photon but not by carbon-ion irradiation.
abstract: OBJECTIVE
  Sublethal doses of photon irradiation (IR) are suspected to increase tumor cell migration and support locoregional recurrence of disease, which has already been shown in other cell lines. This manuscript describes the effect of photon and carbon-ion IR on WHO class I meningioma cell migration and provides an approach to the underlying cellular mechanisms.
  
  
  METHODS
  Meningioma cells were gained operatively at the university hospital in Homburg/Saar, Germany. For migration, membranes (8-µm pore sizes) were coated with collagen I, with collagen IV, and with fibronectin. Cells were analyzed in migration experiments with or without serum stimulation, with or without photon and carbon IR 24 h prior to experiments, and with or without integrin antibodies. Fluorescence-activated cell sorting (FACS) analyses of the integrins ανβ1, ανβ3, and ανβ5 were performed without IR and 6, 12 and 24 h after IR. Enzyme-linked immunosorbent assay (ELISA) analyses of matrix metalloproteinases (MMP)-2 and MMP-9 were realized with and without IR after cells were cultured on collagen I, collagen IV, or fibronectin for 24 h. Cells and supernatants for FACS and ELISA were stored at - 18 °C. The significance level was set at 5 % using both Student's t test and two-way ANOVA.
  
  
  RESULTS
  Migration of meningioma cells was serum-inducible (p < 0.001). It could be increased by photon IR (p < 0.02). The integrins ανβ1 and ανβ5 showed a 21 and 11 % higher expression after serum stimulation (not significant), respectively, and ανβ1 expression was raised by 14 % (p = 0.0057) after photon IR. Antibody blockage of the integrins ανβ1 and ανβ5 inhibited serum- and photon-induced migration. Expression of MMP-2 and MMP-9 remained unchanged after both IR and fetal bovine serum (FBS). Carbon-ion IR left both integrin expression and meningioma cell migration unaffected.
  
  
  CONCLUSIONS
  Photon but not carbon-ion IR promotes serum-based meningioma cell migration. Fibronectin receptor integrin ανβ1 signaling can be identified as an important mechanism for serum- and photon-induced migration of WHO class I meningioma cells.
authors.affiliation: Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany, florian.simon@hotmail.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Simon
authors.forename: Jan-Oliver
authors.initials: JO
authors.lastname: Dittmar
authors.forename: Stephan
authors.initials: S
authors.lastname: Brons
authors.forename: Lena
authors.initials: L
authors.lastname: Orschiedt
authors.forename: Steffi
authors.initials: S
authors.lastname: Urbschat
authors.forename: Klaus-Josef
authors.initials: KJ
authors.lastname: Weber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
authors.forename: Stefan
authors.initials: S
authors.lastname: Rieken
mesh_terms: D002244:Carbon; D002465:Cell Movement / Q000276:immunology* / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D006801:Humans; D039564:Integrin alphaV / Q000276:immunology*; D008577:Meningeal Neoplasms / Q000276:immunology* / Q000473:pathology; D008579:Meningioma / Q000276:immunology* / Q000473:pathology; D011522:Protons; D011829:Radiation Dosage
chemical_list: D039564:Integrin alphaV; D011522:Protons; D002244:Carbon