ecm regulates mt1mmp localization with beta1 or alphavbeta3 integrins at distinct cell compartments modulating its internalization and activity on human endothelial cells regulation of membranetype 1 matrix metalloproteinase mt1mmp by different extracellular matrices ecms on human endothelial cells ecs has been investigated first mt1mmp is found at the intercellular contacts of confluent ecs grown on beta1 integrindependent matrix such as type 1 collagen col i fibronectin fn or fibrinogen fg but not on gelatin gel or vitronectin vn the novel localization of mt1mmp at cellcell contacts is assessed by confocal videomicroscopy of mt1mmpgfptransfected ecs moreover mt1mmp colocalizes with beta1 integrins at the intercellular contacts whereas it is preferentially found with alphavbeta3 integrin at motilityassociated structures on migrating ecs in addition clustered integrins recruit mt1mmp and neutralizing antibeta1 or antialphav integrin mab displace mt1mmp from its specific sites pointing to a biochemical association that is finally demonstrated by coimmunoprecipitation assays on the other hand col i fn or fg upregulate cell surface mt1mmp on confluent ecs by an impairment of its internalization whereas expression and internalization are not modified on gel or vn in addition mt1mmp activity is diminished in confluent ecs on col i fn or fg finally mt1mmp participates and cooperates with beta1 and alphavbeta3 integrins in the migration of ecs on different ecm these data show a novel mechanism by which ecm regulates mt1mmp association with beta1 or alphavbeta3 integrins at distinct cellular compartments thus modulating its internalization activity and function on human ecs