ROLE OF INTEGRIN ALPHA-2-BETA (VLA-2) IN THE MIGRATION OF HUMAN-MELANOMA CELLS ON LAMININ AND TYPE-IV COLLAGEN

The random cell migration of four human melanoma cell lines on laminin and type IV collagen - coated substrates was studied by video time-la pse image analysis and compared to the expression of a number of beta1 integrins including alpha1beta1, alpha2beta1, alpha3beta1, and alpha6 beta1 using flow cytometry. These integrins were heterogeneously expre ssed in the four cell lines tested with three of four lines expressing alpha2beta1. The melanoma cell line that did not express alpha2beta1, exhibited weak attachment and low cell migration rate on both laminin and type IV collagen, whereas the other melanoma cell lines showed an increase in attachment and mean cell migration rate in a dose-depende nt manner on the matrix molecules (p < 0.001). The enhanced migration seen in the three cell lines could be specifically inhibited by functi on blocking anti-beta1 and anti-2 monoclonal antibodies (p < 0.001) bu t not by function blocking anti-alpha3 and anti-alpha6 monoclonal anti bodies. Image analysis of the cells before and after treatment with an ti-beta1 and anti-alpha2 MoAb indicated that the inhibition of migrati on did not result in detectable cell detachment, retraction of cell pr ocesses, or other significant cell-shape change. Taken together, the f indings suggest that the observable enhanced migration on laminin and type IV collagen of a number of human melanoma cell lines is largely m ediated by integrin alpha2beta1.