title: Development of tissue-engineered models of oral dysplasia and early invasive oral squamous cell carcinoma.
abstract: BACKGROUND
  Current organotypic models of dysplasia and oral squamous cell carcinoma (OSCC) lack the complexity that mimics in vivo tissue. Here we describe a three-dimensional in vitro model of the oral epithelium that replicates tumour progression from dysplasia to an invasive phenotype.
  
  
  METHODS
  The OSCC cell lines were seeded as a cell suspension (D20, Cal27) or as multicellular tumour spheroids (FaDu) with oral fibroblasts on to a de-epidermised acellular dermis to generate tissue-engineered models and compared with patient biopsies.
  
  
  RESULTS
  The D20 and Cal27 cells generated a model of epithelial dysplasia. Overtime Cal27 cells traversed the basement membrane and invaded the connective tissue to reproduce features of early invasive OSCC. When seeded onto a model of the normal oral mucosa, FaDu spheroids produced a histological picture mimicking carcinoma in situ with severe cellular atypia juxtaposed to normal epithelium.
  
  
  CONCLUSIONS
  It is possible to culture in vitro models with the morphological appearance and histological characteristics of dysplasia and tumour cell invasion seen in vivo using native dermis. Such models could facilitate study of the molecular processes involved in malignant transformation, invasion and tumour growth as well as in vitro testing of new treatments, diagnostic tests and drug delivery systems for OSCC.
authors: Academic Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, Sheffield S10 2TA, UK. h.colley@sheffield.ac.uk
authors: H E
authors: HE
authors: Colley
authors: V
authors: V
authors: Hearnden
authors: A V
authors: AV
authors: Jones
authors: P H
authors: PH
authors: Weinreb
authors: S M
authors: SM
authors: Violette
authors: S
authors: S
authors: Macneil
authors: M H
authors: MH
authors: Thornhill
authors: C
authors: C
authors: Murdoch
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology*; D023822:Tissue Engineering