Matrix metalloproteinases and cellular motility in development and disease

The movement of cells and the accompanied remodeling of the extracellular matrix is a critical step in many developmental processes. The matrix metalloproteinases (MMPs) are well recognized as mediators of matrix degradation, and their activity as regulators of signaling pathways by virtue of the cleavage of nonmatrix substrates has been increasingly appreciated. In this review, we focus on the role of MMPs in altering processes that influence cellular motility. MMP involvement in cellular adhesion, lamellipodia-directed movement, invadopodial protrusion, axonal growth cone extension, and chemotaxis are discussed. Although not designed to be comprehensive, these examples clearly demonstrate that cellular regulation of the MMPs influences cell motility in a variety of ways, including regulating cell-cell interactions, cell-matrix interactions, matrix degradation, and the release of bioactive signaling molecules. Deregulation of these interactions can ultimately result in disorders including inflammatory diseases, vascular diseases, bone diseases, neurological disorders, and cancer.