Interference with the Complement System by Tumor Cell Membrane Type-1 Matrix Metalloproteinase Plays a Significant Role in Promoting Metastasis in Mice

2006 ◽  
Vol 66 (12) ◽  
pp. 6258-6263 ◽  
Author(s):  
Dmitri V. Rozanov ◽  
Alexei Y. Savinov ◽  
Vladislav S. Golubkov ◽  
Stephen Tomlinson ◽  
Alex Y. Strongin
2004 ◽  
Vol 279 (45) ◽  
pp. 46551-46557 ◽  
Author(s):  
Dmitri V. Rozanov ◽  
Alexei Y. Savinov ◽  
Vladislav S. Golubkov ◽  
Tatiana I. Postnova ◽  
Albert Remacle ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Annette Arndt ◽  
Klaus Kraft ◽  
Eva Wardelmann ◽  
Konrad Steinestel

Colorectal cancer (CRC) is one of the leading causes of death from cancer in the western world, but tumor biology and clinical course show great interindividual variation. Molecular and morphologic tumor characteristics, such asKRAS/BRAFmutation status, mismatch repair (MMR) protein expression, tumor growth pattern, and tumor cell budding, have been shown to be of key therapeutic and/or prognostic relevance in CRC. Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-anchored zinc-binding endopeptidase that is expressed at the leading edge of various invasive carcinomas and promotes tumor cell invasion through degradation of the extracellular matrix. The aim of this study was to investigate possible associations between MT1-MMP expression and molecular tumor characteristics as well as morphologic features of tumor aggressiveness in a consecutive series of 79 CRC tissue samples. However, although MT1-MMP was expressed in 41/79 samples (52%), there was no significant association between MT1-MMP expression andKRAS/BRAFmutation status, MMR protein expression, presence of lymphovascular invasion, tumor growth pattern, tumor-infiltrating lymphocytes, or tumor cell budding in our sample cohort (P>0.05). Thus, we conclude that although MT1-MMP may play a role in CRC invasion, it is not of key relevance to the current models of CRC invasion and aggressiveness.


Surgery ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 142-147 ◽  
Author(s):  
Peter Shamamian ◽  
Ben J.Z. Pocock ◽  
Jess D. Schwartz ◽  
Sara Monea ◽  
Neal Chuang ◽  
...  

Surgery ◽  
1998 ◽  
Vol 124 (2) ◽  
pp. 232-238 ◽  
Author(s):  
Jess D. Schwartz ◽  
Peter Shamamian ◽  
Sara Monea ◽  
David Whiting ◽  
Stuart G. Marcus ◽  
...  

2001 ◽  
Vol 153 (5) ◽  
pp. 893-904 ◽  
Author(s):  
Masahiro Kajita ◽  
Yoshifumi Itoh ◽  
Tadashige Chiba ◽  
Hidetoshi Mori ◽  
Akiko Okada ◽  
...  

Migratory cells including invasive tumor cells frequently express CD44, a major receptor for hyaluronan and membrane-type 1 matrix metalloproteinase (MT1-MMP) that degrades extracellular matrix at the pericellular region. In this study, we demonstrate that MT1-MMP acts as a processing enzyme for CD44H, releasing it into the medium as a soluble 70-kD fragment. Furthermore, this processing event stimulates cell motility; however, expression of either CD44H or MT1-MMP alone did not stimulate cell motility. Coexpression of MT1-MMP and mutant CD44H lacking the MT1-MMP–processing site did not result in shedding and did not promote cell migration, suggesting that the processing of CD44H by MT1-MMP is critical in the migratory stimulation. Moreover, expression of the mutant CD44H inhibited the cell migration promoted by CD44H and MT1-MMP in a dominant-negative manner. The pancreatic tumor cell line, MIA PaCa-2, was found to shed the 70-kD CD44H fragment in a MT1-MMP–dependent manner. Expression of the mutant CD44H in the cells as well as MMP inhibitor treatment effectively inhibited the migration, suggesting that MIA PaCa-2 cells indeed use the CD44H and MT1-MMP as migratory devices. These findings revealed a novel interaction of the two molecules that have each been implicated in tumor cell migration and invasion.


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