Bradykinin promotes vascular endothelial growth factor expression and increases angiogenesis in human prostate cancer cells.

Abstract

Prostate cancer is the most commonly diagnosed malignancy in men and shows a tendency for metastasis to distant organs. Angiogenesis is required for metastasis. Bradykinin (BK) is an inflammatory mediator involved in tumor growth and metastasis, but its role in vascular endothelial growth factor (VEGF) expression and angiogenesis in human prostate cancer remains unknown. The aim of this study was to examine whether BK promotes prostate cancer angiogenesis via VEGF expression. We found that exogenous BK increased VEGF expression in prostate cancer cells and further promoted tube formation in endothelial progenitor cells and human umbilical vein endothelial cells. Pretreatment of prostate cancer with B2 receptor antagonist or small interfering RNA (siRNA) reduced BK-mediated VEGF production. The Akt and mammalian target of rapamycin (mTOR) pathways were activated after BK treatment, and BK-induced VEGF expression was abolished by the specific inhibitor and siRNA of the Akt and mTOR cascades. BK also promoted nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) activity. Importantly, BK knockdown reduced VEGF expression and abolished prostate cancer cell conditional medium-mediated angiogenesis. Taken together, these results indicate that BK operates through the B2 receptor, Akt, and mTOR, which in turn activate NF-κB and AP-1, activating VEGF expression and contributing to angiogenesis in human prostate cancer cells.

• Authors: Hsin-Shan Yu, Shih-Wei Wang, An-Chen Chang, Huai-Ching Tai, Hung-I Yeh, Yu-Min Lin, Chih-Hsin Tang
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 87 Issue 2 Pg. 243-53 (Jan 15 2014) ISSN: 1873-2968 [Electronic] England
• PMID: 24225154 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Bradykinin

Topics

• Bradykinin (physiology)
• Cells, Cultured
• Gene Expression Regulation, Neoplastic
• Human Umbilical Vein Endothelial Cells
• Humans
• Male
• Neovascularization, Pathologic (pathology, physiopathology)
• Prostatic Neoplasms (metabolism)
• Vascular Endothelial Growth Factor A (agonists, biosynthesis)