Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

Matrix metalloproteases (MMPs) are a multigene family of zinc-dependent endopeptidases, which are secreted as latent pro-enzymes and have the capacity to degrade components of the extracellular matrix (ECM) following activating cleavage. In addition, MMPs have the ability to process molecules such as growth factors, receptors, adhesion molecules, other proteinases and proteinase inhibitors. MMPs are basically divided into distinct subclasses according to their substrate specificity and cellular localization: the secreted soluble collagenases, gelatinases, stromelysins and matrilysins; and the membrane-type MMPs which are integral plasma membrane proteins capable of activating MMPs. For certain family members, including some of the membrane-associated MMPs, activating cleavage can be achieved intracellularly by the protease furin. For other MMPs, however, activation is executed by extracellular proteases such as plasmin or other MMPs. While restricted to only a small number of normal cells, several MMPs are overexpressed by different kinds of solid tumors and have been implicated in the ECM degradation associated with tumor growth, angiogenesis and invasiveness [435] [436] [437] [438] [439] .