title: Targeting ανβ3 and ανβ5 inhibits photon-induced hypermigration of malignant glioma cells.
abstract: BACKGROUND
  Sublethal photon irradiation was recently suspected to increase tumor cell motility and promote locoregional recurrence of disease. This study was set up to describe mechanisms underlying increased glioma cell migration through photon irradiation and to analyse the modifiability of photon-altered glioma cell motility by integrin inhibition.
  
  
  METHODS
  Eight μm pore size membranes were coated with vitronectin (VN), collagen I and collagen IV. U87 and Ln229 glioma cells were analysed in migration experiments with and without radiotherapy (RT), serum stimulation and addition of monoclonal antibodies directed to human integrins ανβ3 and ανβ5. Quantitative FACS analysis of integrins was performed in U87 and Ln229 glioma cells following RT. Statistical analysis was performed using Student's t-test.
  
  
  RESULTS
  Glioma cell migration is serum-dependent and can be increased by photon RT which leads to enhanced expression of Vn receptor integrins. Blocking of either ανβ3 or ανβ5 integrins by antibodies inhibits Vn-based migration of both untreated and photon-irradiated glioma cells.
  
  
  CONCLUSIONS
  Peripheral glioma cells are at risk of attraction into the adjacent healthy brain by serum components leaking through the blood brain barrier (BBB). Radiation therapy is associated with upregulation of Vn receptor integrins and enhanced glioma cell migration at sublethal doses. This effect can be inhibited by specific integrin blockade. Future therapeutical benefit may be derived from pharmacological integrin inhibition in combination with photon irradiation.
authors: University Hospital of Heidelberg, Department of Radiation Oncology, Heidelberg, Germany. Stefan.rieken@med.uni-heidelberg.de
authors: Stefan
authors: S
authors: Rieken
authors: Daniel
authors: D
authors: Habermehl
authors: Angela
authors: A
authors: Mohr
authors: Lena
authors: L
authors: Wuerth
authors: Katja
authors: K
authors: Lindel
authors: Klaus
authors: K
authors: Weber
authors: Jürgen
authors: J
authors: Debus
authors: Stephanie E
authors: SE
authors: Combs
mesh_terms: D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D002469:Cell Separation; D024042:Collagen Type I / Q000096:biosynthesis; D024141:Collagen Type IV / Q000096:biosynthesis; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D017785:Photons; D019030:Receptors, Vitronectin / Q000378:metabolism*; D012306:Risk; D019096:Vitronectin / Q000096:biosynthesis
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D039302:Integrin alphaVbeta3; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5