Increased incidence of matrix metalloproteinases in urine of cancer patients

MA Moses, D Wiederschain, KR Loughlin… - Cancer Research, 1998 - AACR
MA Moses, D Wiederschain, KR Loughlin, D Zurakowski, CC Lamb, MR Freeman
Cancer Research, 1998AACR
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 …
Abstract
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 ≥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.
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