Each functional TMEM doorway comprises three different cell types in direct and stable physical contact: a tumor cell highly expressing the actin-regulatory protein Mammalian-enabled (MENA), a tumor-associated macrophage expressing high levels of perivascular tyrosine kinase with immunoglobulin-like loops and epidermal growth factor homology domains 2 (TIE2) and VEGF (TIE2hi/VEGFhi) macrophage and an angiopoietin 2 (ANG2) secreting endothelial cell [56,57]. Here, TEK is linked to neoplasm.