ALTERED CELL-MATRIX CONTACT - A PREREQUISITE FOR BREAST-CANCER METASTASIS

The integrins are receptors that regulate interaction between epitheli al cells and the extracellular matrix. Previous studies have shown tha t a reduction in the expression of the alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, alpha v beta 1 and alpha v beta 5 integrins in primar y breast cancer is associated with positive nodal status. In order to assess the functional significance of altered integrin expression, pri mary breast cancer cells were derived from individual patients with kn own tumour characteristics using immunomagnetic separation. Purified h uman fibronectin, vitronectin, laminin and type IV collagen were used to represent the principal extracellular matrix proteins in an in vitr o adhesion assay. Primary breast cancer cells from lymph node-positive patients were significantly less adhesive to each of the matrix prote ins studied (P<0.001, Mann;Whitney U-test). Matrix adhesion of primary breast cancer cells from node-negative patients was inhibited by appr opriate integrin monoclonal antibodies (P<0.001, paired Wilcoxon test) . Adhesion to fibronectin, vitronectin and laminin, but not type IV co llagen, was influenced by the inhibitor arginine-glycine-aspartate, su ggesting that breast cancer cell recognition of collagen IV is mediate d through alternative epitopes, Weak matrix adhesion correlated with l oss of integrin expression in tissue sections from corresponding patie nts assessed using immunohistochemistry. This study demonstrates a lin k between altered integrin expression and function in primary breast c ancers predisposed to metastasize.