title: Cathepsin B in human myometrium and in uterine leiomyomas at various stages of tumour growth.
abstract: OBJECTIVE
  Cathepsin B is a major cysteine protease involved in the degradation of extracellular matrix proteins, as well as in the activation of precursor forms of other proteases and in release of matrix-bound growth factors. We assessed the expression and activity of cathepsin B, and the inhibitory effect of cysteine protease inhibitors in human myometrium and uterine leiomyomas at various stages of tumour growth.
  
  
  METHODS
  Studies were performed on human myometrium collected from 12 patients and on uterine leiomyomas of various weights: small (less than or equal to 25 g, taken from 10 patients) and large (more than or equal to 100 g, obtained from 13 patients). Tissue extracts were assayed for cathepsin B activity and for inhibitory effect of cysteine protease inhibitors against papain using fluorogenic substrates, and calculated per DNA content. Statistical analysis was performed by Kruskal-Wallis analysis of variance followed by Dunn's post hoc tests. The enzyme expression was evaluated by SDS/polyacrylamide gel electrophoresis followed by Western immunoblotting.
  
  
  RESULTS
  In all the investigated tissues cathepsin B exists mainly in a fully processed double-chain form. The enzyme activity and expression were similar in control myometrium and in small leiomyomas. However, they distinctly increased during tumour growth. The effect of cysteine protease inhibitors was comparable in all the tissues examined.
  
  
  CONCLUSIONS
  These data suggest that the enhanced activity and expression of cathepsin B but not the action of cysteine protease inhibitors contribute to an increased remodelling of extracellular matrix and bioavailability of various growth factors, which favour leiomyoma growth.
authors.affiliation: Department of Medical Biochemistry, Medical University of Bialystok, Poland. Electronic address: tgogiel@umb.edu.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gogiel
authors.affiliation: Department of Medical Biochemistry, Medical University of Bialystok, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Wolańska
authors.affiliation: Department of Medical Biochemistry, Medical University of Bialystok, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Galewska
authors.affiliation: Department of Gynaecology, District General Hospital in Bialystok, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kinalski
authors.affiliation: Department of Medical Biochemistry, Medical University of Bialystok, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sobolewski
authors.affiliation: Department of Medical Biochemistry, Medical University of Bialystok, Poland.
authors.forename: Lech
authors.initials: L
authors.lastname: Romanowicz
mesh_terms: D002401:Cathepsin B / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism* / Q000473:pathology; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D015853:Cysteine Proteinase Inhibitors; D002401:Cathepsin B
keywords: Cathepsin B; Extracellular matrix; Human myometrium; Uterine leiomyoma