TY - JOUR
T1 - Cell surface association of matrix metalloproteinase-9 (gelatinase B)
AU - Fridman, Rafael
AU - Toth, Marta
AU - Chvyrkova, Irina
AU - Meroueh, Samy O.
AU - Mobashery, Shahriar
PY - 2003/6
Y1 - 2003/6
N2 - 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.
AB - 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.
KW - Cell surface binding
KW - Matrix metalloproteinase
KW - Protease
KW - Zymogen
UR - http://www.scopus.com/inward/record.url?scp=0038702661&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038702661&partnerID=8YFLogxK
U2 - 10.1023/A:1023091214123
DO - 10.1023/A:1023091214123
M3 - Review article
C2 - 12784994
AN - SCOPUS:0038702661
SN - 0167-7659
VL - 22
SP - 153
EP - 166
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
IS - 2-3
ER -