Abstract
Abstract Bradykinin (BK) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. In addition, bradykinin has been found in many tumor cell lines and has been shown to be involved in carcinogenesis and cancer progression. Prostate cancer is the most common cancer excluding skin cancer in men and usually metastasizes to the particular organs in the late stages of cancer processes. The matrix metalloproteinase (MMP) play an important role in tissue remodeling associated with various physiological and pathological processes such as morphogenesis, angiogenesis, tissue repair, cirrhosis, arthritis and metastasis. In this study, we found that bradykinin increased the migration and the expression of MMP-9 in human prostate cancer cells (PC3,DU145 and LNCaP). Bradykinin-mediated migration and matrix MMP-9 up-regulation was attenuated by bradykinin B2 receptor antagonist (HOE140), protein kinase Cdelta (PKCdelta) inhibitor (Rottlerin), c-Src inhibitor (PP2), NF-kappaB inhibitor (PDTC), and IkappaB protease inhibitor (TPCK). Transfection of cells with bradykinin B2 receptor and protein kinase Cdelta (PKCdelta), siRNA or dominant-negative mutant of c-Src, IkappaBalpha kinase alpha(IKK alpha) and IkappaBalpha kinase beta(IKK beta), also inhibited the potentiating action of bradykinin. Stimulation of PC3 cells with bradykinin induced PKCdelta, c-Src, IKK alpha/beta, IkappaB and p65 phosphorylation, and kappaB-luciferase activity. In addition, BKR2 PCKdelta and c-Src pathways are involved in bradykinin-induced NFkappaB activation. Taken together, our results suggest that bradykinin enhances the migration of prostate carcinoma cells by increasing MMP9 expression through the bradykinin B2 receptor /PKCdelta/c-Src/NF-kappaB signal transduction pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1396. doi:10.1158/1538-7445.AM2011-1396
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