Modulation of very late activation-2 laminin receptor function in breast cancer metastasis.

Abstract

Very late activation-2 (VLA-2) is an integrin receptor for laminin that consists of an alpha 2- and a beta 1-subunit. In human breast cancer, down-regulation of VLA-2 expression is related to positive nodal status. The functional significance of altered integrin expression in individual patients has never been investigated. To test the hypothesis that less adhesive primary breast cancer cells were predisposed to metastasize, variation in VLA-2 modulation of cell attachment to laminin with nodal status was studied. Integrin expression was measured by means of immunohistochemistry on cryostat sections. Primary breast cancer cells were isolated by enzymatic disaggregation and immunomagnetic separation. Cell adhesion to laminin was evaluated in an in vitro assay, and the effect of monoclonal antibodies against the component subunits of VLA-2 was assessed. Adhesion of primary breast cancer cells from women with positive nodes to laminin was significantly reduced compared with women with negative nodes (p < 0.001, Wilcoxon signed rank test). VLA-2 antibodies inhibited primary breast cancer cell attachment of women with negative nodes but not women with positive nodes. Strong adhesion to laminin was related to node-negative status (chi-squared, 16.33; p < 0.001) and to positive integrin expression (chi-squared, 31.54; p < 0.001). VLA-2-mediated adhesion of primary breast cancer cells to laminin differs with nodal status. Measurement of VLA-2 expression may thus be of clinical value as a prognostic indicator in the assessment of breast cancer.