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Increased Incidence of Matrix Metalloproteinases in Urine of Cancer Patients¹

Laboratory for Surgical Research [M. A. M., D. W.], The Urologic Laboratory, Department of Urology [M. R. F.], and Department of Research Computing [D. Z.], Children's Hospital, Boston, Massachusetts 02115; Division of Urological Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115 [K. R. L.]; Department of Radiation Oncology, Beth Israel Hospital, Boston, Massachusetts 02115 [C. C. L.]; and Joint Center for Radiation Therapy and Departments of Radiology [C. C. L., D. Z.] and Surgery [M. A. M., K. R. L., M. R. F.], Harvard Medical School, Boston, Massachusetts 02115

Matrix metalloproteinases (MMPs) have been implicated in mechanisms of metastasis in experimental cancer models and in human malignancies. In this study, we used substrate gel electrophoresis (zymography) to determine the frequency of detection of MMPs in urine of patients with a variety of cancers. Three molecular weight classes of urinary MMPs, M_r 72,000, M_r 92,000, and high molecular weight (M_r 150,000) species, were detected reproducibly and correlated with disease status. The M_r 72,000 and M_r 92,000 species were identified as MMP-2 and MMP-9, respectively, by Western blot analysis. The presence of biologically active MMP-2 (P < 0.001) or MMP-9 (P = 0.002) was an independent predictor of organ-confined cancer, and the high molecular weight species (P < 0.001) was an independent predictor of metastatic cancer. This is the first study to demonstrate that analysis of urinary MMPs may be useful in determining disease status in a variety of human cancers, both within and outside of the urinary tract.

¹ This work was supported by grants from CaPCURE (to M. A. M. and M. R. F.) and the Cancer Research Foundation of America.

² To whom requests for reprints should be addressed, at Enders Research Laboratories, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115. Fax: (617) 355-7043; E-mail: moses_m@al.tch.harvard.edu.

Received 1/19/98. Accepted 2/18/98.

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