Cell adhesion molecules in the normal and cancerous mammary gland

Abstract

Loss of normal tissue morphology is one of the first changes seen in the development of solid malignant tumours, including breast cancers. Since cell adhesion molecules play a crucial role in maintaining normal tissue architecture, investigations into the molecular mechanisms involved in the morphological changes occurring in malignancy that focus on the expression and function of cell adhesion molecules in malignant progression are extremely relevant. This review discusses the cadherin and integrin families of adhesion molecules which have been shown to be extremely important in the cell-cell and cell-matrix interactions of epithelial cells. Immunohistochemical studies using tissue and tumour sections indicate that a reduction in levels of expression or function of both types of cell adhesion molecules is indeed observed in many breast cancers. A specific and crucial role for these molecules in the maintenance of normal morphological differentiation has been demonstrated in vitro, where the noninvasive differentiated phenotype correlates with the normal functioning of E-Cadherin and alpha 2 beta 1 integrin. Further in vitro evidence suggests that in mammary epithelial cells, oncogenes may be upstream regulators of both the expression and function of E-Cadherin, the alpha 2 beta 1 integrin, and other epithelial specific molecules important for maintaining epithelial differentiation. In this way they could manifest their effects on the tumorigeneic potential of epithelial cells.