In coculture of MDA-MB-231 cells (green) with human lung microvascular endothelial cells (labeled by VE-cadherin, red), tumor cell–derived TIMP-2 activates MMP-2 from endothelial cells, leading to endothelial barrier opening and paracellular gap formation. Note that tumor cells tend to transmigrate through intercellular spaces where cell-cell junctions (VE-cadherin, red) are loosened or sequestrated. The endothelial barrier response is considerably reduced during inhibition of MMP-2 or MMP-14. For further details, please see Shen and coworkers on page 939 in this issue.