Cell surface association of matrix metalloproteinase-9 (gelatinase B)

• Published in: Cancer and metastasis reviews 2003-06, Vol.22 (2-3), p.153-166
• Main Authors: Fridman, Rafael, Toth, Marta, Chvyrkova, Irina, Meroueh, Samy O, Mobashery, Shahriar
• Format: Article
• Language: English
• Subjects: Cell Membrane - enzymology; Enzyme Activation; Extracellular Matrix - enzymology; Humans; Matrix Metalloproteinase 9 - metabolism; Receptors, Cell Surface - metabolism
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1023/A:1023091214123

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.