title: Increased levels of macrophage-secreted cathepsin S during prostate cancer progression in TRAMP mice and patients.
abstract: BACKGROUND
  Protein expression during prostate tumour progression in transgenic TRAMP mice was studied, with the aim of identifying proteins associated with tumour progression and castration resistant tumour growth.
  
  
  METHODS
  Protein expression was compared between normal mouse prostate, primary TRAMP tumours and peripheral metastases in long-term castrated TRAMP mice using 2-dimensional differential in-gel electrophoresis and MALDI TOF/TOF analysis. Results were verified with Western blot analysis and immunohisto-chemistry in the TRAMP model and samples from patients.
  
  
  RESULTS
  The active form of cathepsin S (Cat S) was identified as being significantly up-regulated in poorly differentiated TRAMP tumours and in castration-resistant metastases compared to normal mouse prostate and well-differentiated tumours. Increased Cat S levels were also found in high Gleason grade tumour areas in patients. Cat S was primarily expressed by tumour-infiltrating macrophages, as shown by double staining of Cat S and CD68 expressing cells. A significantly higher number of Cat S expressing macrophages was found in castration-resistant than in hormone naïve high grade tumours in patients. No relation was found between Cat S levels and suggested Cat S regulated, matrix-derived fragments of collagen IV or laminin 5 gamma2.
  
  
  CONCLUSIONS
  Macrophage-secreted Cat S levels increase during prostate cancer progression and could be an interesting target for therapy.
authors.affiliation: Department of Medical Biosciences, Pathology, Umeå University, Umeå, S-90187 Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Lindahl
authors.forename: Monika
authors.initials: M
authors.lastname: Simonsson
authors.forename: Anders
authors.initials: A
authors.lastname: Bergh
authors.forename: Elin
authors.initials: E
authors.lastname: Thysell
authors.forename: Henrik
authors.initials: H
authors.lastname: Antti
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.forename: Pernilla
authors.initials: P
authors.lastname: Wikström
mesh_terms: D000818:Animals; D019393:Arrestin / Q000378:metabolism; D002369:Castration; D002403:Cathepsins / Q000378:metabolism*; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism
chemical_list: D019393:Arrestin; C400567:LAMC2 protein, human; D007797:Laminin; D002403:Cathepsins; C028217:cathepsin S