title: Enhanced urinary gelatinase activities (matrix metalloproteinases 2 and 9) are associated with early-stage bladder carcinoma: a comparison with clinically used tumor markers.
abstract: Matrix metalloproteinases (MMPs) are involved in tumor growth and metastasis, promoting the migration and invasion of cells. In this study, the amount of MMP-2 and MMP-9 activity was measured in urine from superficial bladder carcinoma patients (pTa, pT1) to evaluate their possible diagnostic value. The active and total amount of MMP-2 and MMP-9, respectively, in urine from tumor patients were compared with the levels in urine from age- and gender-matched healthy volunteers. Both MMP-2 and MMP-9 activity levels were significantly enhanced in urine from patients with high invasive cancers (pT2, PT3), whereas in urine from healthy controls no or very low MMP activities were found. More importantly, a substantial number of urine samples from patients with superficial tumors contained elevated MMP-2 and MMP-9 activities, suggesting that enhanced urinary MMP activity levels, indeed, might be indicative for early-stage bladder cancer. Overall, urinary MMP-2 and MMP-9 activity levels were significantly correlated to each other, with some individual exceptions. A comparison between urinary MMP-9 activity and a recently proposed urinary marker for bladder cancer, NMP-22, showed slightly lower numbers of patients with elevated levels for MMP-9. But because MMP-9 and NMP-22 levels were not correlated, enhanced urinary MMP activity might be useful as a marker for superficial bladder carcinoma like, or especially in combination with, other markers.
authors.affiliation: Department of Molecular Pathology and Medicine DIBIT, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: C F
authors.initials: CF
authors.lastname: Sier
authors.forename: G
authors.initials: G
authors.lastname: Casetta
authors.forename: J H
authors.initials: JH
authors.lastname: Verheijen
authors.forename: A
authors.initials: A
authors.lastname: Tizzani
authors.forename: V
authors.initials: V
authors.lastname: Agape
authors.forename: J
authors.initials: J
authors.lastname: Kos
authors.forename: F
authors.initials: F
authors.lastname: Blasi
authors.forename: R
authors.initials: R
authors.lastname: Hanemaaijer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D002277:Carcinoma / Q000175:diagnosis* / Q000652:urine*; D016022:Case-Control Studies; D002401:Cathepsin B / Q000652:urine; D003404:Creatinine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000652:urine*; D014568:Urokinase-Type Plasminogen Activator / Q000652:urine
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22; D003404:Creatinine; D014568:Urokinase-Type Plasminogen Activator; D002401:Cathepsin B; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9