Abstract
Extracellular proteases are recognized as critical factors in the progression of a number of carcinomas, including prostate cancer. Matrix metalloproteases (MMP) are important in processes of tumor growth, invasion and dissemination, but other classes of proteases, such as serine and cysteine proteases, also contribute. We utilized the TRAMP model for prostate cancer to elucidate proteases involved in prostate cancer progression. General proteomic analysis was performed on normal murine prostate, early TRAMP tumors and advanced TRAMP tumors, as well as normal and involved lymph nodes. Zymography and antigenic analyses revealed increased expression of mainly pro-MMP in early TRAMP tumors but substantial elaboration of activated MMP only in late TRAMP tumors. Progressive increase in cysteine, serine and certain membrane-bound proteases from normal to early to advanced prostate tumors, was also seen. Our results implicate pericellular proteases as initiators of major proteolytic cascades during tumor progression and suggest targets for maximal therapeutic effect.
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Acknowledgements
We thank Drs Zena Werb and Mark Sternlicht for anti-MMP-2 and MMP-9 antibodies, Drs Charles Craik and Toshi Takeuchi for antibody to MT-SP1, and Dr Lynn Matrisian for the gift of anti-MMP-7 antibody. This publication was made possible by funds received from the Cancer Research Fund, under Interagency Agreement #97–12013 (University of California, Davis contract #98–00924V) with the Department of Health Services, Cancer Research Section, and from NIH/NHLBI P01 CA72006.
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Bok, R., Hansell, E., Nguyen, T. et al. Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model. Prostate Cancer Prostatic Dis 6, 272–280 (2003). https://doi.org/10.1038/sj.pcan.4500676
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DOI: https://doi.org/10.1038/sj.pcan.4500676
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