PURPOSE: We have previously reported that matrix metalloproteinases MMP-2, MMP-9, and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. In addition, we also detected several unidentified urinary gelatinase activities with molecular weights >125 kDa. The objective of the current study was to identify these high molecular weight (HMW) species, determine their potential as predictors of disease status, and ask whether a tumor-specific pattern existed based on urinary MMP analysis. EXPERIMENTAL DESIGN: Chromatography, zymography, and mass spectrometry was used to identify HMW gelatinase species of approximately 140, 190, and >220 kDa in urine of cancer patients. To determine whether a tumor-specific pattern of appearance existed among the MMPs detected, we analyzed the urine of 189 patients with prostate or bladder cancer and controls. RESULTS: The approximately 140, >220 kDa, and approximately 190 HMW gelatinase species were identified as MMP-9/tissue inhibitor of metalloproteinase 1 complex, MMP-9 dimer, and ADAMTS-7, respectively. The frequency of detection of any MMP species was significantly higher in urine from prostate and bladder cancer groups than controls. MMP-9 dimer and MMP-9 were independent predictors for distinguishing between patients with prostate and bladder cancer (P < 0.001 for each) by multivariable analysis. CONCLUSIONS: This study is the first to identify a tumor-specific urinary MMP fingerprint that may noninvasively facilitate identification of cancer presence and type. This information may be of diagnostic and prognostic value in the detection and/or clinical monitoring of disease progression and therapeutic efficacy in patients with bladder or prostate cancer.
PURPOSE: We have previously reported that matrix metalloproteinases MMP-2, MMP-9, and the complex MMP-9/NGAL can be detected in urine of patients with a variety of cancers including prostate and bladder carcinoma. In addition, we also detected several unidentified urinary gelatinase activities with molecular weights >125 kDa. The objective of the current study was to identify these high molecular weight (HMW) species, determine their potential as predictors of disease status, and ask whether a tumor-specific pattern existed based on urinary MMP analysis. EXPERIMENTAL DESIGN: Chromatography, zymography, and mass spectrometry was used to identify HMW gelatinase species of approximately 140, 190, and >220 kDa in urine of cancerpatients. To determine whether a tumor-specific pattern of appearance existed among the MMPs detected, we analyzed the urine of 189 patients with prostate or bladder cancer and controls. RESULTS: The approximately 140, >220 kDa, and approximately 190 HMW gelatinase species were identified as MMP-9/tissue inhibitor of metalloproteinase 1 complex, MMP-9 dimer, and ADAMTS-7, respectively. The frequency of detection of any MMP species was significantly higher in urine from prostate and bladder cancer groups than controls. MMP-9 dimer and MMP-9 were independent predictors for distinguishing between patients with prostate and bladder cancer (P < 0.001 for each) by multivariable analysis. CONCLUSIONS: This study is the first to identify a tumor-specific urinary MMP fingerprint that may noninvasively facilitate identification of cancer presence and type. This information may be of diagnostic and prognostic value in the detection and/or clinical monitoring of disease progression and therapeutic efficacy in patients with bladder or prostate cancer.
Authors: B Davies; J Waxman; H Wasan; P Abel; G Williams; T Krausz; D Neal; D Thomas; A Hanby; F Balkwill Journal: Cancer Res Date: 1993-11-15 Impact factor: 12.701
Authors: Tracy T Batchelor; Dan G Duda; Emmanuelle di Tomaso; Marek Ancukiewicz; Scott R Plotkin; Elizabeth Gerstner; April F Eichler; Jan Drappatz; Fred H Hochberg; Thomas Benner; David N Louis; Kenneth S Cohen; Houng Chea; Alexis Exarhopoulos; Jay S Loeffler; Marsha A Moses; Percy Ivy; A Gregory Sorensen; Patrick Y Wen; Rakesh K Jain Journal: J Clin Oncol Date: 2010-05-10 Impact factor: 44.544
Authors: Neil S Horowitz; Richard T Penson; Dan G Duda; Emmanuelle di Tomaso; Yves Boucher; Marek Ancukiewicz; Kenneth S Cohen; Suzanne Berlin; Carolyn N Krasner; Marsha A Moses; Rakesh K Jain Journal: Clin Ovarian Cancer Other Gynecol Malig Date: 2011-06
Authors: William H Chappell; Stephen L Abrams; Richard A Franklin; Michelle M LaHair; Giuseppe Montalto; Melchiorre Cervello; Alberto M Martelli; Ferdinando Nicoletti; Saverio Candido; Massimo Libra; Jerry Polesel; Renato Talamini; Michele Milella; Agostino Tafuri; Linda S Steelman; James A McCubrey Journal: Cell Cycle Date: 2012-11-16 Impact factor: 4.534