The activation, expression and function of gelatinase A (MMP-2)

Gelatinase A is a member of the Matrix Metalloproteinase (MMP) family. These enzymes are usually secreted as latent pro-enzymes, are activated by proteolytic cleavage of an amino terminal domain, and are inhibited by tissue inhibitor of metalloproteinases (TIMPs). They are involved in extracellular matrix remodeling, both in normal processes of growth and development, and in pathological processes such as tumor invasion and metastasis. Gelatinase A has a number of distinctive characteristics, that suggest it may play a unique role in these processes. Unlike most MMPs it is constitutively expressed by many cells and has a ubiquitous tissue distribution. Another unique feature is that this protease is activated on the cell surface by the recently discovered membrane-type MMP (MT-MMP). Expression of gelatinase A correlates with the aggressiveness of many tumors, which suggests that it may be a useful prognostic indicator, as well as a suitable target for anti-cancer therapies.