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Bradykinin enhances cell migration in human prostate cancer cells through B2 receptor/PKCδ/c-Src dependent signaling pathway

Authors

  • Hsin-Shan Yu,

    1. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
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  • Tien-Huang Lin,

    1. Department of Urology, Buddhist Tzu Chi General Hospital Taichung Branch, Taichung, Taiwan
    2. School of Chinese Medicine, China Medical University, Taichung, Taiwan
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  • Chih-Hsin Tang

    Corresponding author
    1. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
    2. Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
    • Department of Pharmacology, School of Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan.
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  • All authors have no financial or personal relationships with other people or organizations that could inappropriately influence our work.

Abstract

BACKGROUND

Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. Bradykinin (BK) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. The aim of this study was to investigate whether Bradykinin is associated with migration of prostate cancer cells.

METHODS

Cancer cells migration activity was examined using the Transwell assay. The c-Src and PKCδ phosphorylation was examined by using Western blot method. The qPCR was used to examine the mRNA expression of metalloproteinase. A transient transfection protocol was used to examine NF-κB activity.

RESULTS

We found that bradykinin increased the chemomigration and the expression of MMP-9 of human prostate cancer cells. Bradykinin-mediated chemomigration and metalloproteinase expression was attenuated by PKCδ inhibitor (rottlerin), PKCδ siRNA, c-Src inhibitor (PP2) and c-Src mutant. Activations of PKCδ, c-Src and NF-κB pathways after bradykinin treatment was demonstrated, and bradykinin-induced expression of metalloproteinase and chemomigration activity was inhibited by the specific inhibitor and mutant of PKCδ, c-Src, and NF-κB cascades.

CONCLUSIONS

This study showed for the first time that the bradykinin mediates migration of human prostate cancer cells. One of the mechanisms underlying bradykinin directed migration was transcriptional up-regulation of MMP-9 and activation of B2 receptor, PKCδ, c-Src, and NF-κB pathways. Prostate 73: 89–100, 2013. © 2012 Wiley Periodicals, Inc.

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