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. MATERIALS AND 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. CONCLUSION: Macrophage-secreted Cat S levels increase during prostate cancer progression and could be an interesting target for therapy.
BACKGROUND: Protein expression during prostate tumour progression in transgenic TRAMPmice was studied, with the aim of identifying proteins associated with tumour progression and castration resistant tumour growth. MATERIALS AND METHODS: Protein expression was compared between normal mouse prostate, primary TRAMPtumours and peripheral metastases in long-term castrated TRAMPmice 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 TRAMPtumours 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. CONCLUSION: Macrophage-secreted Cat S levels increase during prostate cancer progression and could be an interesting target for therapy.
Authors: Vasilena Gocheva; Hao-Wei Wang; Bedrick B Gadea; Tanaya Shree; Karen E Hunter; Alfred L Garfall; Tara Berman; Johanna A Joyce Journal: Genes Dev Date: 2010-01-15 Impact factor: 11.361
Authors: J A Gormley; S M Hegarty; A O'Grady; M R Stevenson; R E Burden; H L Barrett; C J Scott; J A Johnston; R H Wilson; E W Kay; P G Johnston; S A Olwill Journal: Br J Cancer Date: 2011-10-11 Impact factor: 7.640
Authors: Richard D A Wilkinson; Andrew Young; Roberta E Burden; Rich Williams; Christopher J Scott Journal: Mol Cancer Date: 2016-04-21 Impact factor: 27.401