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http://hdl.handle.net/1956/2632
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| Tittel: | Epithelial-mesenchymal interactions in normal and neoplastic human oral mucosa : a study on in vitro organotypic models |
| Forfattere: | Costea, Daniela Elena |
| Dato: | 15-Apr-2005 |
| Forlag: | The University of Bergen |
| Sammendrag: | Epithelial-mesenchymal interactions are necessary for the development of oral
epithelium during embryogenesis, but adult oral epithelium is also under the influence of
mesenchymal tissue in both normal and neoplastic conditions. The aim of this study was
to investigate the role of fibroblasts on morphogenesis of normal and neoplastic human
oral epithelium. In vitro organotypic models of normal, early neoplastic and neoplastic
human oral mucosa have been developed (Papers I and III). The cultured tissues
obtained in the laboratory were assessed by morphometry, immunohistochemistry and
the TUNEL method. Our data showed that fibroblasts had a crucial effect on cell growth
and differentiation of the reconstituted normal human oral epithelium. Epithelial growth,
but not differentiation could be restored by keratinocyte growth factor (KGF), one of the
soluble factors synthesised by them. A novel finding was that fibroblasts were essential
for restoring the normal pattern of cell death in reconstituted normal human oral
epithelium (Paper II). The studies done on step-wise models of oral carcinogenesis
showed that the role of fibroblasts on epithelial growth was maintained during in vitro
tumour progression (Papers III and IV). In contrast, the tight control exerted by
fibroblasts on epithelial differentiation and cell death of in vitro reconstituted normal
human oral epithelium was gradually lost during in vitro neoplastic progression (Paper
III). Furthermore, our results pointed to an important role for the keratinocyte-fibroblast
cross talk and fibroblast-derived diffusible factors in triggering local invasiveness of early
neoplastic oral keratinocytes. An interesting finding was the species-specificity of
fibroblasts required for the invasive growth of early neoplastic keratinocytes to occur
(Paper IV). This finding brings some concerns on the sensitivity of the in vivo
xenotransplantation method as single test system for identifying putative malignant
human neoplastic cells. In conclusion, this study brings in vitro evidence for the role of
fibroblasts in coordinating the major biological processes of the suprajacent epithelium in
both normal and neoplastic human oral mucosa. |
| URI: | http://hdl.handle.net/1956/2632 |
| ISBN: | 82-8006-022-7 (print version) |
| Vises i samlingene: | Centre for International Health
Department of Oral Sciences
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