TY - JOUR
T1 - Cellular membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves C3b, an essential component of the complement system
AU - Rozanov, Dmitri V.
AU - Savinov, Alexei Y.
AU - Golubkov, Vladislav S.
AU - Postnova, Tatiana I.
AU - Remacle, Albert
AU - Tomlinson, Stephen
AU - Strongin, Ales Y.
PY - 2004/11/5
Y1 - 2004/11/5
N2 - Neoplasms have developed numerous strategies to protect themselves against the host immune system. Membrane type-1 matrix metalloproteinase (MT1-MMP) is strongly associated with many cancer types and is up-regulated in the aggressive, metastatic neoplasms. During the past few years, there has been an increasing appreciation of the important, albeit incompletely understood, role of MT1-MMP in cancer. We have discovered, using cell-free and cell-based assays in vitro, that MT1-MMP proteolysis specifically targets C3b, an essential component of the complement propagation pathway. MT1-MMP proteolysis liberates the deposited C3 activation fragments from the cell surface. The shedding of these cell-deposited opsonins by MT1-MMP inhibits the complement cascade and protects breast carcinoma MCF7 cells from direct complement-mediated injury in the in vitro tests. The functional link associating MT1-MMP with the host immune system, heretofore unrecognized, may empower tumors with an escape mechanism that contributes to the protection against the host antitumor immunity as well as to the survival of invading and metastatic malignant cells in the bloodstream.
AB - Neoplasms have developed numerous strategies to protect themselves against the host immune system. Membrane type-1 matrix metalloproteinase (MT1-MMP) is strongly associated with many cancer types and is up-regulated in the aggressive, metastatic neoplasms. During the past few years, there has been an increasing appreciation of the important, albeit incompletely understood, role of MT1-MMP in cancer. We have discovered, using cell-free and cell-based assays in vitro, that MT1-MMP proteolysis specifically targets C3b, an essential component of the complement propagation pathway. MT1-MMP proteolysis liberates the deposited C3 activation fragments from the cell surface. The shedding of these cell-deposited opsonins by MT1-MMP inhibits the complement cascade and protects breast carcinoma MCF7 cells from direct complement-mediated injury in the in vitro tests. The functional link associating MT1-MMP with the host immune system, heretofore unrecognized, may empower tumors with an escape mechanism that contributes to the protection against the host antitumor immunity as well as to the survival of invading and metastatic malignant cells in the bloodstream.
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U2 - 10.1074/jbc.M405284200
DO - 10.1074/jbc.M405284200
M3 - Article
C2 - 15381670
AN - SCOPUS:8744244478
SN - 0021-9258
VL - 279
SP - 46551
EP - 46557
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -