The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis

Metalloproteases are important in many aspects of biology, ranging from cel l proliferation, differentiation and remodeling of the extracellular matrix (ECM) to vascularization and cell migration. These events occur several ti mes during organogenesis in both normal development and during tumor progre ssion. Mechanisms of metalloprotease action underlying these events include the proteolytic cleavage of growth factors so that they can become availab le to cells not in direct physical contact, degradation of the ECM so that founder cells can move across tissues into nearby stroma, and regulated rec eptor cleavage to terminate migratory signaling. Most of these processes re quire a delicate balance between the functions of matrix metalloproteases ( MMPs) or metalloprotease-disintegrins (ADAMs) and natural tissue inhibitors of metalloproteases (TIMPs). In this review, we discuss recent progress in identifying an essential role for metalloproteases in axon outgrowth, as a n example of a focal invasive event. We also discuss the evolving concept o f how MMPs might regulate stem cell fate during tumor development.