Increased Incidence of Matrix Metalloproteinases in Urine of Cancer Patients1

Matrix metalloproteinases (MMPs) have been implicated in mecha nisms of metastasis in experimental cancer models and in human malig nancies. 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, .*/,. 72,000, \/, 92,000, and high molecular weight (,V/,.£150,000) species, were detected reproducibly and correlated with disease status. The Vi, 72,000 and .)/,. 92,000 species were identified as MMP-2 and MMP-9, respec tively, 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 (/' < 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.