Transmembrane proteases in cell growth and invasion: new contributors to angiogenesis?

Transmembrane proteases (TPs) are proteins anchored in the plasma membrane with their catalytic site exposed to the external surface of the membrane. TPs are widely expressed, and their dysregulated expression is associated with cancer, infection, inflammation, autoimmune and cardiovascular diseases, all diseases where angiogenesis is part of the pathology. TPs participate in extracellular proteolysis (degradation of extracellular matrix components, regulation of chemokine activity, release of membrane-anchored cytokines, cytokine receptors and adhesion molecules) and influence cell functions (growth, secretion of angiogenic molecules, motility). Recent attention has been focused on the ADAM-17 (a disintegrin and metalloprotease)/TACE/CD156q, the MT1-MMP (membrane-type-1 matrix metallo proteinase)/MMP-14, and the ectopeptidases aminopeptidase N (APN/CD13), dipeptidyl peptidase IV (DPPIV/CD26) and angiotensin-converting enzyme (ACE/CD143), that appear to have a critical role in angiogenesis. This article summarizes current knowledge on these TPs, and reviews recent investigations that document their participation during angiogenic-related events. Through their multiple roles, TPs may thereby provide critical links in angiogenesis.