title: Modelling of normal and premalignant oral tissue by using the immortalised cell line, SVpgC2a: a review of the value of the model.
abstract: Normal oral keratinocytes (NOKs), and a Simian virus 40 T-antigen-immortalised oral keratinocyte line termed SVpgC2a, were cultured in an effort to model the human oral epithelium in vitro, including normal and dysplastic tissue. Monolayer and organotypic cultures of NOKs and SVpgC2a were successfully established in a standardised serum-free medium with high levels of amino acids, by using regular tissue culture plastic for monolayers and collagen gels containing oral fibroblasts as the base for generating tissue equivalents. NOKs express many characteristics of normal tissue, including those associated with terminal squamous differentiation. After > 150 passages, SVpgC2a cells retained an immortal, nontumourigenic phenotype that, relative to NOKs, was associated with aberrant morphology, enhanced proliferation, deficiency in terminal differentiation, proneness to apoptosis, and variably altered expression of structural epithelial markers. Transcript and protein profiling, as well as activity assays, demonstrated the expression of multiple xenobiotic-metabolising enzymes in SVpgC2a cells, some of which were higher in comparison to NOKs. A generally preserved, or even activated, ability for xenobiotic metabolism in long-term cultures of SVpgC2a cells indicated that this cell line could be useful in safety testing protocols--for example, in the development of consumer products in the oral health care field. However, SVpgC2a cells displayed some features reminiscent of a severe oral dysplasia, implying that this cell line could also to some extent serve as a model of a premalignant oral epithelium.
authors.affiliation: Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Staab
authors.forename: Martin
authors.initials: M
authors.lastname: Vondracek
authors.forename: Hipolito
authors.initials: H
authors.lastname: Custodio
authors.forename: Katarina
authors.initials: K
authors.lastname: Johansson
authors.forename: Jan Anders
authors.initials: JA
authors.lastname: Nilsson
authors.forename: Peter
authors.initials: P
authors.lastname: Morgan
authors.forename: Jan-Olov
authors.initials: JO
authors.lastname: Höög
authors.forename: Ian
authors.initials: I
authors.lastname: Cotgreave
authors.forename: Roland C
authors.initials: RC
authors.lastname: Grafström
mesh_terms: D000952:Antigens, Polyomavirus Transforming; D002461:Cell Line, Transformed / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D008954:Models, Biological; D009055:Mouth / Q000166:cytology*; D011230:Precancerous Conditions / Q000473:pathology; D018675:Toxicity Tests
chemical_list: D000952:Antigens, Polyomavirus Transforming