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-lapse image analysis and compared to the expression of a number of beta1 integrins including alpha1beta1, alpha2beta1, alpha3beta1, and alpha6beta1 using flow cytometry. These integrins were heterogeneously expressed 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-dependent manner on the matrix molecules (p < 0.001). The enhanced migration seen in the three cell lines could be specifically inhibited by function blocking anti-beta1 and anti-2 monoclonal antibodies (p < 0.001) but not by function blocking anti-alpha3 and anti-alpha6 monoclonal antibodies. Image analysis of the cells before and after treatment with anti-beta1 and anti-alpha2 MoAb indicated that the inhibition of migration did not result in detectable cell detachment, retraction of cell processes, or other significant cell-shape change. Taken together, the findings suggest that the observable enhanced migration on laminin and type IV collagen of a number of human melanoma cell lines is largely mediated by integrin alpha2beta1.