title: Cell surface association of matrix metalloproteinase-9 (gelatinase B).
abstract: Matrix metalloproteinase (MMP)-9 (gelatinase B) belongs to the MMP family of zinc-dependent endopeptidases that has been associated with tumor cell invasion and metastasis and tumor-induced angiogenesis. As a secreted MMP, pro-MMP-9 is released into the extracellular environment by both tumor and stroma cells, where it fulfills its proteolytic functions degrading both extracellular matrix (ECM) and non-ECM proteins. A major dilemma in our understanding of MMP-9 function is how the released protease is targeted to the right location and how its activity is controlled at the pericellular space. It has been proposed that MMP-9 interact with cell surface components and that this type of interaction positively regulates enzymatic activation and activity. However, recent evidence shows that association of MMP-9 with the cell surface is mediated by a distinct array of surface proteins that serve to regulate multiple aspects of the enzyme function including localization, inhibition and internalization. How these distinct mechanisms regulate the overall MMP-9 activity at the pericellular space remains an important goal in our understanding of MMP-9 function at the cell surface. Furthermore, the study of surface-associated MMP-9 imposes new conceptual and methodological challenges with particular consideration to the unique structural and functional characteristics of this key enzyme.
authors.affiliation: Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. rfridman@med.wayne.edu
authors.forename: Rafael
authors.initials: R
authors.lastname: Fridman
authors.forename: Marta
authors.initials: M
authors.lastname: Toth
authors.forename: Irina
authors.initials: I
authors.lastname: Chvyrkova
authors.forename: Samy O
authors.initials: SO
authors.lastname: Meroueh
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000201:enzymology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D020780:Matrix Metalloproteinase 9