| 1. |
- Lindahl, Charlotta, et al.
(författare)
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Increased levels of macrophage-secreted Cathepsin S during Prostate Cancer progression in TRAMP mice and patients
- 2009
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Ingår i: Cancer Genomics and Proteomics. - : The International Institute of Anticancer Research. - 1109-6535 .- 1790-6245. ; 6:3, s. 149-159
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Tidskriftsartikel (refereegranskat)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. 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 γ2. Conclusion: Macrophage-secreted Cat S levels increase during prostate cancer progression and could be an interesting target for therapy.
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| 2. |
- Öhlund, Daniel, 1979-, et al.
(författare)
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Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer
- 2009
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 101:1, s. 91-97
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients. METHODS: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques. RESULTS: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival. CONCLUSION: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.
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