Urinary gelatinase activities (matrix metalloproteinases 2 and 9) in human bladder tumors.
The ability to degrade type IV collagen, the major component of the basement membrane, is unique to gelatinases A and B. These two matrix metalloproteinases (MMPs) are most often linked to the malignant phenotype of tumor cells, and their expression is elevated in several cases of human tumor aggressiveness and overall survival. By gelatin zymography, we verified MMP activity in the urine of patients with bladder cancer. Of these patients, 10 had well-, 8 had moderately and 7 had poorly differentiated bladder cancer. The urine of healthy volunteers with no evidence of disease was used for controls. Zymography showed five dominant gelatinolytic bands of 240, 220, 130, 92 and 72 kDa in tumor samples, whereas only traces of MMP were detected in the urine of healthy subjects. The majority of cancerous urine samples showed MMP-9 lytic activity but only a few contained MMP-2. Moreover, MMP-9 content is enhanced in the urine from patients with high-grade and advanced-stage bladder tumors. Finally, we determined the urinary levels of urinary bladder cancer (UBC), tissue polypeptide-specific antigen (TPS) and protein 22 of nuclear matrix (NMP22). The levels of TPS and NMP-22 were higher in G3 bladder cancer than in G1 and G2 neoplasias. The urinary values of these two biomarkers correlated with the increase in MMP-9 lytic activity in high-grade and advanced-stage bladder cancer.
Di Carlo
Angelina
A
Dipartimento di Medicina Sperimentale e Patologia, Università di Roma La Sapienza, 00161 Roma, Italy.
Terracciano
Daniela
D
Mariano
Angela
A
Macchia
Vincenzo
V
D000230:Adenocarcinoma / Q000201:enzymology / Q000652:urine*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine; D016022:Case-Control Studies; D002401:Cathepsin B / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000652:urine*; D020780:Matrix Metalloproteinase 9 / Q000652:urine*; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000652:urine; D010455:Peptides / Q000652:urine; D001743:Urinary Bladder / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000652:urine*; D014568:Urokinase-Type Plasminogen Activator / Q000652:urine
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D010455:Peptides; C100379:nuclear matrix protein 22; C089984:tissue polypeptide specific antigen; D014568:Urokinase-Type Plasminogen Activator; D002401:Cathepsin B; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9