Jones, Judith; (1996) The expression and function of integrins in malignant oral epithelium. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

Integrins are cell surface molecules involved in cell-cell and cell-extracellular matrix interactions. They consist of non-covalently linked α and β glycoprotein chains, and play an important role in regulating cellular interactions during growth, development, differentiation and the immune response as well as tumour cell invasion and metastasis. Altered integrin expression has been reported in various epithelial tumours as well as epithelial cell lines derived from them. However, the effect that altered integrin expression has on the behaviour of epithelial cells is not fully understood. The purpose of this study was to investigate the role of integrins in modulating the behaviour of keratinocytes. Epithelial cell lines derived from oral squamous cell carcinomas (SCCs) were used along with frozen sections of oral squamous cell carcinomas. SCC cell lines H357 and H376 that were naturally deficient in the αv and β4 integrin subunits respectively were "repaired" by transfection of the cell line with the missing subunit along with a drug resistance gene. Empty vector controls were also made. Positive clones were sorted by FACS, until after 4 sorts stable integrin expression was observed in 7 αv and 5 β4 clones. β5 was the subunit found to be associated with the αv subunit. Introduction of the integrin subunits had no consistent effect on the growth rate of the clones on tissue culture plastic. However, anchorage-independent growth was reduced in the αv expressing clones compared with the negative controls. Neither positive transfectants nor parental cells caused tumour formation in nude mice. The capacity for terminal differentiation, as measured by involucrin production, a precursor of the cornified envelope of keratinocytes, was increased in the αv clones, but not in the β4 clones. Expression of the αvβ5 and α6β4 integrins in the cell lines enabled them to adhere to their respective ligands, vitronectin and laminin. Expression of a6B4 reduced the motility of the H376 cells. Staining of frozen sections of oral squamous cell carcinomas showed a reduction in αvβ5 and αv in poorly differentiated tumours compared with moderately and well differentiated tumours. β6 was only expressed in squamous cell carcinomas whereas β3 was not expressed in any of the specimens examined.

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