Objectives: To investigate a potential role of oral fibroblasts on tumour progression of early neoplastic oral epithelial cells. Methods: In vitro organotypic models of early neoplastic human oral mucosa were developed, by growing an established cell line of dysplastic human oral keratinocytes (DOK-ECACC 94122104) on top of connective tissue equivalents/matrixes. To investigate the growth and invasive potential of DOK cells, two types of matrixes were prepared: simple collagen matrix and primary human fibroblast containing matrix. Epithelial growth (total epithelial thickness and cell proliferation index: IHC with Ki67Mib-1Ab) and invasiveness (depth and area of invasion: histomorphometry) were assessed. Results: Epithelial thickness and cell proliferation rate were significantly higher (p<0.05) when DOK were cultured on top of fibroblast containing matrixes (81.3 ± 6.7 mm and 22.9 ± 1.2%) than DOK cultured on top of simple collagen gels (51.1 ± 4.6 mm and 15.1 ± 0.38 %). The presence of fibroblasts in the matrix induced an extensive local invasion (depth 95.6 ± 7.1 mm and area of invasion 50.8 ± 4.1%), while a minimal invasion was noticed when DOK were grown on simple collagen gels (14.2 ± 2.1mm and 5.0 ± 0.8 % p<0.05). Addition of conditioned media from parallel cultures with human fibroblast containing matrix, or addition of known human growth factors, restored the growth of DOK cells on simple collagen gels (p>0.05 when compared with DOK grown on human fibroblast containing matrix). Local invasion was also induced by conditioned media from parallel cultures with human fibroblasts containing matrix (p<0.05). However, the induced invasion only partially restored the depth and invasive area found in cultures with fibroblast containing matrix (p<0.05). Conclusions: The growth and invasiveness of early neoplastic oral epithelial cells were dependent on fibroblast support. Moreover, diffusible human growth factors could fully restore the neoplastic growth and partially the local invasion.

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