title: Endothelin-1 stimulates oral fibroblasts to promote oral cancer invasion.
abstract: OBJECTIVE
  The aims of this study were to examine the role of endothelin-1 (ET-1), a pleiotropic peptide found at elevated levels in a number of malignancies and which has been shown to influence oral cancer cell behaviour via paracrine signalling pathways, on the phenotype of oral fibroblasts.
  
  
  METHODS
  The effect of ET-1 on proliferation and migration of human primary oral fibroblasts was assessed using MTS and scratch assays, respectively. The ability of ET-1 to affect fibroblast contractility was analysed using type-I collagen gels. Changes in gene expression in oral fibroblasts exposed to ET-1 were examined using quantitative PCR. The invasiveness of oral cancer cells in the presence of conditioned media collected from ET-1 treated fibroblasts was determined using 2D Matrigel assays.
  
  
  RESULTS
  Here we provide evidence that ET-1 increases the migration of oral fibroblasts and induces a more contractile phenotype which is not associated with changes in gene expression indicative of myofibroblast transdifferentiation. In addition we provide evidence that conditioned medium of ET-1-stimulated oral fibroblasts promotes invasion of OSCC cells in vitro.
  
  
  CONCLUSIONS
  In oral squamous cell carcinoma, a frequently fatal and increasingly common epithelial malignancy of the oral cavity, ET-1 is known to contribute to pro-migratory paracrine signalling between stromal fibroblasts and cancer cells. The ability of ET-1 to modulate the phenotype of human oral stromal fibroblasts, however, has not previously been reported. The findings presented here suggest that targeting the stromal endothelin system may be a viable and novel therapeutic strategy for invasive oral cancer.
authors.affiliation: Oral Disease Research Group, School of Clinical Dentistry, University of Sheffield, Sheffield S10 2TA, UK.
authors.forename: E E
authors.initials: EE
authors.lastname: Hinsley
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: K D
authors.initials: KD
authors.lastname: Hunter
authors.forename: S A
authors.initials: SA
authors.lastname: Whawell
authors.forename: D W
authors.initials: DW
authors.lastname: Lambert
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D019899:Paracrine Communication; D051381:Rats; D013623:Tail
chemical_list: D019332:Endothelin-1; D003094:Collagen