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Expression of Membrane-Type Matrix Metalloproteinase in Human Gastric Carcinomas¹

Departments of Molecular Immunology and Pathology [H. N., Y. O.], Surgery [H. N., M. M.], and Molecular Virology and Oncology [H. S., M. S.], Cancer Research Institute, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920, Japan

We have examined the implications of membrane-type matrix metalloproteinase (MT-MMP) for activation of the zymogen of MMP-2 (proMMP-2) in human gastric carcinoma. Northern blot analysis demonstrated exclusive expression of MT-MMP in the carcinoma tissues. Immunohistochemically, MT-MMP was colocalized in the carcinoma cells in almost all MMP-2-positive cases (13 of 14 cases). Gelatin zymography of the culture media showed a correlation of the proMMP-2 activation with MT-MMP expression in the carcinoma cells. A microdissection study indicated that proMMP-2 activation is caused only in the carcinoma cell nests that express MT-MMP but not in the normal gastric mucosa. These results are the first demonstration of the MT-MMP-assisted activation of proMMP-2 in the human gastric carcinoma.

¹ Supported by the Hokkoku Foundation for Cancer Research and Grant-in-Aid 06281107 from the Ministry of Education, Science and Culture, of Japan (to Y. O.).

² To whom requests for reprints should be addressed.

Received 4/28/95. Accepted 6/16/95.

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