Adhesion molecules in breast cancer: role of alpha 2 beta 1 integrin

An early event in the development of breast carcinomas is the loss of normal tissue architecture. In benign lesions and in situ tumours both luminal and myoepithelial cells are present, but in most invasive cancers the malignant cell has the phenotype of the luminal cell, and proliferates without contacting the myoepithelial cells or the basement membrane. The reduction in cell contacts is clearly crucial for the initiation of metastatic growth, and is accompanied by a loss of expression or function of cell adhesion molecules. Immunohistochemical studies using tissue and tumour sections indicate that a decrease in the level of expression of the alpha 2 beta 1 integrin is observed in many breast cancers. A specific and crucial role for this molecule in the maintenance of normal morphological differentiation has also been demonstrated in in vitro studies. The evidence from these studies suggests that, in mammary epithelial cells, oncogenes may be upstream regulators of the expression of the alpha 2 beta 1 integrin and of other specific molecules important for epithelial differentiation. These findings implicate oncogenes in the initial events relating to the disruption of tissue architecture that is seen in invasive breast cancer.