Increased incidence of matrix metalloproteinases in urine of cancer patients.

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, Mr 72,000, Mr 92,000, and high molecular weight (Mr > or = 150,000) species, were detected reproducibly and correlated with disease status. The Mr 72,000 and Mr 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]  Papers that report diagnostic or screening tests , 1998 .

[2]  S. Kamidono,et al.  Elevation of serum levels of matrix metalloproteinase‐2 and ‐3 as new predictors of recurrence in patients with urothelial carcinoma , 1996, Cancer.

[3]  T. Stamey,et al.  A comparison of the free fraction of serum prostate specific antigen in men with benign and cancerous prostates: the best case scenario. , 1996, The Journal of urology.

[4]  M. Nakajima,et al.  Prognostic significance of circulating matrix metalloproteinase-2 to tissue inhibitor of metalloproteinases-2 ratio in recurrence of urothelial cancer after complete resection. , 1996, Cancer research.

[5]  R. Bast,et al.  Ovarian cancer screening. The use of serial complementary tumor markers to improve sensitivity and specificity for early detection , 1995, Cancer.

[6]  J. van Nagell,et al.  Ovarian cancer screening , 1991, Cancer.

[7]  J. Woessner.  The Family of Matrix Metalloproteinasesa , 1994 .

[8]  D. Isenberg,et al.  Serum metalloproteinases and their inhibitors: markers for malignant potential. , 1994, British Journal of Cancer.

[9]  M A Moses,et al.  Retinoids modulate endothelial cell production of matrix-degrading proteases and tissue inhibitors of metalloproteinases (TIMP). , 1994, The Journal of biological chemistry.

[10]  J. Richie,et al.  Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. , 1994, Journal of the National Cancer Institute.

[11]  Serum and plasma M(r) 92,000 progelatinase levels correlate with spontaneous metastasis of rat 13762NF mammary adenocarcinoma. , 1993, Cancer research.

[12]  T R Fleming,et al.  An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer. , 1993, JAMA.

[13]  J. Richie,et al.  Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients. , 1993, Journal of the National Cancer Institute.

[14]  U. Moll,et al.  Mr 92,000 Type IV Collagenase Is Increased in Plasma of Patients with Colon Cancer and Breast Cancer , 1993 .

[15]  L. Liotta,et al.  Urinary type IV collagenase: elevated levels are associated with bladder transitional cell carcinoma. , 1992, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[16]  L. Liotta,et al.  Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy. , 1992, Cancer research.

[17]  E. Howard,et al.  Regulation of the autoactivation of human 72-kDa progelatinase by tissue inhibitor of metalloproteinases-2. , 1991, The Journal of biological chemistry.

[18]  C. Blyth.  Approximate Binomial Confidence Limits , 1986 .

[19]  Z. Werb,et al.  Secretion of metalloproteinases by stimulated capillary endothelial cells. II. Expression of collagenase and stromelysin activities is regulated by endogenous inhibitors. , 1986, The Journal of biological chemistry.

[20]  M. Weinstein,et al.  Clinical Decision Analysis , 1980 .