Integrins and oral cancer

Integrins are a family of heterodimeric, cation-dependent cell membrane adhesion molecules which mediate cell-cell and cell-matrix interactions. They play a fundamental role in the maintenance of tissue integrity and in the regulation of cell proliferation, growth, differentiation and migration. It is not surprising, therefore, that integrins have been implicated in neoplasia and tumour progression and metastasis. Integrin expression and function are altered in malignant cells, although no specific integrin has been implicated in transformation to the malignant phenotype and changes in integrin expression vary both between and within different tumour types. In oral squamous cell carcinomas there is variable loss or reduced expression of beta 1 integrins and of alpha 6 beta 4, which correlates to loss of basement membrane proteins and is most extensive in poorly differentiated lesions. There are also changes in the repertoire of alpha v integrin expression with de novo expression of alpha v beta 6 which may be important in tumour cell migration. Conversely there is reduced expression of alpha v beta 5. In vitro studies suggest that this integrin may be important in oral neoplasia since alpha v-negative cell lines show a malignant phenotype which can be reversed by transfection of the missing integrin. Because alterations in integrin expression in oral cancers are so variable, it seems unlikely that they will be useful as prognostic markers. However, studies of integrin expression and function are increasing our understanding of cell interactions in oral cancer and may pave the way for novel therapeutic interventions to arrest the progression of individual tumours.