Cell surface association of matrix metalloproteinase-9 (gelatinase B).
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.
Fridman
Rafael
R
Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. rfridman@med.wayne.edu
Toth
Marta
M
Chvyrkova
Irina
I
Meroueh
Samy O
SO
Mobashery
Shahriar
S
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*
D011956:Receptors, Cell Surface; D020780:Matrix Metalloproteinase 9