Integrin β 1,-mediated invasion of human breast cancer cells: An ex vivo assay for invasiveness

Background: The integrin cell adhesion molecule (CAM) family is intimately involved in cell adhesion and invasion through tissue basement membranes (BM). As a consequence of the short survival of patient-derived human breast cancer cells, the invasion of such cells has not been previously reported. Our aims were to optimise culture conditions in order to establish a reliable invasion assay and to assess the effect on invasion of perturbations of the β ll integrin receptors. Methods: Pure suspensions of viable carcinoma cells were isolated immunomagnetically from human breast cancer (HBC) samples and introduced onto a replicated glycoprotein BM within an invasion chamber. Degree of invasion was compared to both β 1lintegrin expression and tumour grade. Additionally, the effect of fll receptor blockade with monoclonal antibody (mAb) was assessed. Results: Invasion was significantly greater in grade 11 than grade 111 tumour cells @ = 0.0012). Antiintegrin fil monoclonal antibody inhibited cancer cell invasion by a mean of 83.96 ± 4.80%. Conclusions: The invasion assay confirmed the fundamental importance of fil integrin receptors to transmembrane invasion and reports this for the first time in cells isolated from primary breast cancer. It represents a potent research tool for investigation of the tumour biology of invasion at the integrin β l,-mediated cell-basement membrane interface. This assay has the potential clinical application of improved stratification of patients for adjuvant therapy on a more individual basis than currently available.