MODULATION OF VERY LATE ACTIVATION-2 LAMININ RECEPTOR FUNCTION IN BREAST-CANCER METASTASIS

Background. 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 b reast cancer, down-regulation of VLA-2 expression is related to positi ve nodal status. The functional significance of altered integrin expre ssion in individual patients has never been investigated. To test the hypothesis that less adhesive primary breast cancer cells were predisp osed to metastasize, variation in VLA-2 modulation of cell attachment to laminin with nodal status was studied. Methods. Integrin expression was measured by means of immunohistochemistry on cryostat sections. P rimary breast cancer cells were isolated by enzymatic disaggregation a nd immunomagnetic separation. Cell adhesion to laminin was evaluated i n an in vitro assay, and the effect of monoclonal antibodies against t he component subunits of VLA-2 was assessed. Results. Adhesion of prim ary breast cancer cells from women with positive nodes to laminin was significantly reduced compared with women with negative nodes (p < 0.0 01, Wilcoson signed rank test). VLA-2 antibodies ingibited primary bre ast cancer coll attachment of women with negative nodes but not women with positvie nodes. Strong adhesion to laminin was related to node-ne gative status (chi-wquared, 16.33; p < 0.001) and to positive integrin expression (chi-wquared, 31.54; p < 0.001). Conclusions. VLA-2 mediat ed adhesion of primary breast cancer cells to laminin differs with nod al status. Measurement of VLA-2 expression may thus be of clinical val ue as a prognostic indicator in the assessment of breast cancer.