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Abstract
Metalloproteases are important in many aspects of biology, ranging from cell proliferation,
differentiation and remodeling of the extracellular matrix (ECM) to vascularization
and cell migration. These events occur several times during organogenesis in both
normal development and during tumor progression. Mechanisms of metalloprotease action
underlying these events include the proteolytic cleavage of growth factors so that
they can become available to cells not in direct physical contact, degradation of
the ECM so that founder cells can move across tissues into nearby stroma, and regulated
receptor cleavage to terminate migratory signaling. Most of these processes require
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 an example of a focal invasive event. We also discuss the evolving
concept of how MMPs might regulate stem cell fate during tumor development.