Cellular membrane type-1 matrix metalloproteinase (MT1-MMP) cleaves C3b, an essential component of the complement system.

Abstract

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 anti-tumor immunity as well as to the survival of invading and metastatic malignant cells in the bloodstream.

• Authors: Dmitri V Rozanov, Alexei Y Savinov, Vladislav S Golubkov, Tatiana I Postnova, Albert Remacle, Stephen Tomlinson, Alex Y Strongin
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 45 Pg. 46551-7 (Nov 05 2004) ISSN: 0021-9258 [Print] United States
• PMID: 15381670 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Opsonin Proteins
• Complement C3b
• Complement C4b
• Complement System Proteins
• Matrix Metalloproteinases, Membrane-Associated
• Metalloendopeptidases
• Matrix Metalloproteinase 2

Topics

• Blotting, Western
• Cell Line, Tumor
• Cell Membrane (metabolism)
• Cell Separation
• Cell-Free System
• Complement C3b (metabolism)
• Complement C4b (metabolism)
• Complement System Proteins (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Humans
• Immunoprecipitation
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinases, Membrane-Associated
• Metalloendopeptidases (metabolism, physiology)
• Opsonin Proteins (metabolism)
• Protein Binding
• Time Factors
• Transfection