Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis.

Physiological processes involving remodelling of the extracellular matrix, such as wound healing, embryogenesis, angiogenesis, and the female reproductive cycle, require the activity of matrix metalloproteinases (MMPs). This group of proteases degrades basal membranes and connective tissues and plays an essential role in the homeostasis of the extracellular matrix. An imbalance in the expression or activity of MMPs can have important consequences in diseases such as multiple sclerosis, Alzheimer's disease, or the development of cancers. Because of the pathophysiological importance of MMPs, their activity is highly controlled in order to confine them to specific areas. An activation cascade, initiated by the proteolysis of plasminogen, cleaves proMMPs, and every step is controlled by specific activators or inhibitors. MMPs destabilize the organization of the extracellular matrix and influence the development of cancer by contributing to cell migration, tumor cell proliferation, and angiogenesis. Accordingly, these proteases possess an important role in cell-matrix interactions by affecting fundamental processes such as cell differentiation and proliferation. Therefore, the characterization of MMPs involved in specific types and stages of tumors will significantly improve the diagnosis and treatment of these cancers in humans.