title: Expression of cathepsins B, H, and L and their inhibitors as markers of transitional cell carcinoma of the bladder.
abstract: OBJECTIVE
  It has been shown that the expression of the lysosomal proteolytic enzymes cathepsin B, H, and L (CB, CH, and CL, respectively) correlate with tumor progression in various neoplasms. However, no data are available in cell lysates and supernatants of differently differentiated human bladder cell lines or in noncancerous and cancerous bladder tissue.
  
  
  METHODS
  Using spectrofluorometric assays, catalytic activities of CB, CH, CL, and their inhibitor (CIP) were measured both in differently differentiated human bladder cell lines (HCV29, normal; RT4, well differentiated; J82, poorly differentiated) and in noncancerous and cancerous tissue samples (n = 20) of transitional cell carcinoma obtained from transurethral resections of the bladder or cystectomies. Enzyme activities were related to the protein content in tissue samples or to the cell count in cell lines.
  
  
  RESULTS
  In comparison to the intracellular activities of CB, CH, and CL in the poorly differentiated cell line J82, the intracellular activities in the normal cell line HCV29 were significantly greater (P <0.05), independent of stage or grade. In contrast, the portion of cathepsins released from cell line J82 into the supernatant revealed higher values than that from cell line HCV29. In cancerous bladder tissue, CB and CH were significantly greater than in the matched normal tissue (P <0.05). CL and CIP did not show any statistically significant differences.
  
  
  CONCLUSIONS
  Increased cathepsin concentrations in the supernatant of the poorly differentiated J82 carcinoma cell culture, as well as in cancerous bladder tissue, are indicative of a proteolytic imbalance and potential indicators of bladder cancer.
authors.affiliation: Department of Urology, University Hospital Charité, Humboldt University Berlin, Berlin, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Staack
authors.forename: Diana
authors.initials: D
authors.lastname: Tolic
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schnorr
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Loening
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000201:enzymology* / Q000473:pathology; D002401:Cathepsin B / Q000032:analysis / Q000037:antagonists & inhibitors; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis* / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases / Q000032:analysis; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D009367:Neoplasm Staging; D051381:Rats; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D015853:Cysteine Proteinase Inhibitors; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534280:Ctsl protein, rat; C534126:CTSH protein, human; D056655:Cathepsin H; C534128:Ctsh protein, rat