Literature DB >> 11448063

Membrane-type 1 matrix metalloproteinase enhances lymph node metastasis of gastric cancer.

Y Yonemura1, Y Endo, T Takino, K Sakamoto, E Bandou, K Kinoshita, S Fushida, K Miwa, K Sugiyama, T Sasaki.   

Abstract

The mechanisms of the lymph node metastasis remain unclear. We demonstrate the role of MT1-MMP on the lymph node metastasis using in vivo experimental model of lymph node metastasis by orthotopic implantation of MT1-MMP transfected gastric cancer cell line in the stomach of nude rats. TMK-1 cell line without expression of MT1-MMP was transfected with the pcDNA3 plasmid containing a 3.4-kb MT1-MMP cDNA fragment by calcium phosphate method, and the transfected cell line was designated as TMK-MT. Western blot and RT-PCR analyses showed the specific bands corresponding to MT1-MMP in the TMK-MT cells. By gelatin zymography, the activated form (62-kDa) of MMP-2 was identified in the medium of TMK-MT cell line, but was not detected in TMK-1 cells. Six weeks after orthotopic implantation of TMK-1 and TMK-MT xenografts of nude mouse-subcutaneus tumor into the stomach of nude rats, gastric tumors were found in all the animals. Histologically, the lymphatic invasion was found in the submucosa of the TMK-MT gastric tumors. Lymph node metastasis was not detected in nude rats bearing TMK-1 gastric tumor (0/8). In contrast, lymph node metastasis was detected in five out of 8 rats, bearing TMK-MT gastric tumor. MT1-MMP immunoreactivity was found on the cell membrane and cytoplasm of TMK-MT cells not only in the lymph node metastasis but also in the stomach tumor. These results suggest that MT1-MMP overexpression induced by transfection of its gene may promote lymph node metastasis of transformed cells.

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Year:  2000        PMID: 11448063     DOI: 10.1023/a:1010887014669

Source DB:  PubMed          Journal:  Clin Exp Metastasis        ISSN: 0262-0898            Impact factor:   5.150


  21 in total

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Journal:  Gastric Cancer       Date:  2000-09-29       Impact factor: 7.370

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Journal:  Proc Natl Acad Sci U S A       Date:  1995-03-28       Impact factor: 11.205

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Journal:  Cancer Res       Date:  1995-08-01       Impact factor: 12.701

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5.  Selective function-blocking monoclonal human antibody highlights the important role of membrane type-1 matrix metalloproteinase (MT1-MMP) in metastasis.

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