title: The role of α9β1 integrin in modulating epithelial cell behaviour.
abstract: BACKGROUND
  Integrins initiate signalling in response to the extracellular matrix (ECM), which is important in wound healing and cancer. Previous studies have shown that over-expression of the αvβ6 integrin in oral squamous cell carcinoma (OSCC) cells results in enhanced motility and expression of matrix-degrading proteases, and the aim of this study was to investigate whether this is also the case for the α9β1 integrin.
  
  
  METHODS
  H357 OSCCcells were transfected with the α9 integrin subunit and proliferation, adhesion and migration assays were performed on these along with null vector control and wild-type cells. The effect of ligand engagement on matrix metalloproteinase expression and the plasminogen activator system was measured using ELISA and chromogenic assays. Expression of α9 integrin was examined in oral squamous cell carcinoma tissue by immunohistochemistry.
  
  
  RESULTS
  Functionally active α9 integrin mediated specific upregulation of adhesion and migration towards the TNfn3RAA fragment of tenascin-C but reduced proliferation. Migration towards collagen I was also enhanced in transfected cells. Matrix metalloproteinase-2 and metalloproteinase-9 expression was increased upon TNfn3RAA ligand engagement. Cell surface plasmin generation was also enhanced in α9-expressing cells and was the result of enhanced expression of urokinase receptor. In normal oral mucosa, α9 integrin expression was restricted to the suprabasal and prickle cell layers, and expression was heterogeneous in tumours but present in islands infiltrating connective tissue particularly in moderately and well-differentiated lesions.
  
  
  CONCLUSIONS
  The α9β1 integrin may play a key role in modulation of tumour behaviour including enhanced cell migration and expression of matrix-degrading proteases.
authors: Oral & Maxillofacial Pathology, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, UK.
authors: Sushmita
authors: S
authors: Roy
authors: Lynne
authors: L
authors: Bingle
authors: John F
authors: JF
authors: Marshall
authors: Rosemary
authors: R
authors: Bass
authors: Vincent
authors: V
authors: Ellis
authors: Paul M
authors: PM
authors: Speight
authors: Simon A
authors: SA
authors: Whawell