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M_r 92,000 Type IV Collagenase Is Increased in Plasma of Patients with Colon Cancer and Breast Cancer¹

Departments of Research [S. Z., R. M. L.] and Medicine [S. Z., M. H. Z.], Department of Veterans Affairs Medical Center, Northport, New York 11768, and Department of Medicine [S. Z., M. H. Z.] and Pathology [U. M.], State University of New York at Stony Brook, Stony Brook, New York 11794

Overproduction of matrix metalloproteinases (MMPs) is a common characteristic of metastatic cancer cells. Since MMPs can be identified in plasma, we proposed that enhanced MMP-9 secretion by invasive cancer cells may be detected by plasma assay. To this end, we developed a specific sandwich enzyme-linked immunosorbent assay which uses two mouse monoclonal antibodies to human M_r 92,000 type IV collagenase (MMP-9). The plasma concentration of MMP-9 (mean ± SD) in 60 healthy subjects (9 ± 11 ng/ml), 136 patients without cancer, and 179 patients with cancer of the lung, genitourinary tract, or lymphomas-leukemias did not differ significantly. In contrast, plasma MMP-9 was significantly increased (P < 0.01) in 122 patients with gastrointestinal tract cancer and breast cancer (18 ± 23 and 21 ± 22 ng/ml, respectively). Whereas carcinoembryonic antigen levels were significantly increased in patients with stage IV gastrointestinal cancer, MMP-9 concentrations were not significantly increased in patients with metastatic disease as compared to those with nonmetastatic cancer. Combining both assays improves sensitivity of detection of colon cancer. MMP-9 was also significantly increased during pregnancy which is consistent with the extensive ongoing tissue remodeling and the leaching of the tissue proteinase into plasma.

¹ This research was supported by a grant from the Department of Veterans Affairs, a grant from the Center for Biotechnology, State University of New York at Stony Brook which is sponsored by the New York State Science and Technology Foundation, and the Ann Schermerhom Cancer Foundation.

² To whom requests for reprints should be addressed, at Mail code 151, V.A. Medical Center, Northport, NY 11768.

Received 2/19/92. Accepted 10/20/92.

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