Metastasis requires the presence of three cells in direct contact on a blood vessel wall: a tumor cell that produces the protein MENA; a peri-vascular macrophage (cells that guide tumor cells to blood vessels); and a blood-vessel endothelial cell. The presence of three such cells in contact with each other is called a tumor microenvironment of metastasis, or TMEM, which is depicted within the box in this illustration.