The many faces of metalloproteases: cell growth, invasion, angiogenesis and metastasis.
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.
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Department of Anatomy, Box 0452, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0452, USA.
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D000818:Animals; D001369:Axons / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D011480:Protease Inhibitors / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D006133:Growth Substances; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases