Involvement of intercellular adhesion molecule-1 up-regulation in bradykinin promotes cell motility in human prostate cancers.

Abstract

Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to distant organs. Bradykinin (BK) is an inflammatory mediator and has recently been shown to mediate tumor growth and metastasis. The adhesion molecule intercellular adhesion molecule-1 (ICAM-1) plays a critical role during tumor metastasis. The aim of this study was to examine whether BK promotes prostate cancer cell migration via ICAM-1 expression. The motility of cancer cells was increased following BK treatment. Stimulation of prostate cancer cells with BK induced mRNA and protein expression of ICAM-1. Transfection of cells with ICAM-1 small interfering RNA reduced BK-increased cell migration. Pretreatment of prostate cancer cells with B2 receptor, phosphatidylinositol 3-kinase (PI3K), Akt, and activator protein 1 (AP-1) inhibitors or mutants abolished BK-promoted migration and ICAM-1 expression. In addition, treatment with a B2 receptor, PI3K, or Akt inhibitor also reduced BK-mediated AP-1 activation. Our results indicate that BK enhances the migration of prostate cancer cells by increasing ICAM-1 expression through a signal transduction pathway that involves the B2 receptor, PI3K, Akt, and AP-1. Thus, BK represents a promising new target for treating prostate cancer metastasis.

• Authors: Hsin-Shan Yu, Tien-Huang Lin, Chih-Hsin Tang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 7 Pg. 13329-45 (Jun 26 2013) ISSN: 1422-0067 [Print] Switzerland
• PMID: 23803661 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ICAM1 protein, human
• Neoplasm Proteins
• Vasodilator Agents
• Intercellular Adhesion Molecule-1
• Bradykinin

Topics

• Bradykinin (pharmacology)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Humans
• Intercellular Adhesion Molecule-1 (biosynthesis, genetics)
• Male
• Neoplasm Proteins (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Signal Transduction (drug effects, genetics)
• Up-Regulation (drug effects, genetics)
• Vasodilator Agents (pharmacology)