Roles of Immune-Cell-Derived Matrix Metalloproteinases in Tumor Growth and Metastasis

A considerable amount of clinical and experimental data has shown that proteolytic enzymes affecting the composition and function of the extracellular matrix (ECM) and cell surface molecules appear to be essential for the metastatic process. Certain structural changes of the ECM accompany cell migration during physiological tissue remodeling and tumor cell invasion. The ECM forms basement membranes that modulate cell adhesion, cell motility, and the selective exchange of molecules between cells and interstitial fluids. In mediating immune surveillance, inflammatory cells routinely cross this barrier. Matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that share structural domains and have the capacity to degrade ECM components as well as to alter biological functions of ECM macromolecules (1). The specific proteolytic targets of MMPs include many other proteinases, proteinase inhibitors, clotting factors, chemotactic molecules, latent growth factors, growth-factor-binding proteins, cell surface receptors, as well as cell-cell and cell-matrix adhesion molecules (2–10). ECM fragments of laminin, collagen, and fibrin also have biological roles in modulating inflammatory cell infiltration and cell proliferation. Such activities further underscore the importance of immune-cell-derived matrix-degrading enzymes, such as MMPs, during tumor growth and metastasis.