Increased levels of macrophage-secreted cathepsin S during prostate cancer progression in TRAMP mice and patients.

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.