Patterns of protease production during prostate cancer progression: proteomic evidence for cascades in a transgenic model

被引:20
作者
Bok, RA
Hansell, EJ
Nguyen, TP
Greenberg, NM
McKerrow, JH
Shuman, MA
机构
[1] Univ Calif San Francisco, Med Ctr, Dept Med, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pathol & Pharmaceut Chem, San Francisco, CA 94143 USA
[3] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA
关键词
proteases; prostate cancer; extracellur transgenic proteomics; PLASMINOGEN-ACTIVATOR; SERINE-PROTEASE; CELLULAR-LOCALIZATION; UROKINASE RECEPTOR; CLINICAL-TRIALS; EXPRESSION; INHIBITOR; INCREASES; GROWTH; TISSUE;
D O I
10.1038/sj.pcan.4500676
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:272 / 280
页数:9
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