BLT2 promotes the invasion and metastasis of aggressive bladder cancer cells through a reactive oxygen species-linked pathway

Eun Young Kim, Ji Min Seo, Cheolmin Kim, Jung Eun Lee, Kyung Mi Lee, Jae Hong Kim

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Aggressive bladder cancer is a major cause of morbidity and mortality. Despite the fact that metastatic disease results in death in the majority of bladder cancer cases, the molecular events regulating the invasive phenotype of aggressive bladder cancer are not well understood. In this study, immunohistochemical examination showed that the leukotriene B4 receptor BLT2 is overexpressed in advanced malignant bladder cancers (human transitional cell carcinomas) in proportion to advancing stages, with high prognostic significance (p<0.001). Blockade of BLT2 with the specific antagonist LY255283 or siRNA knockdown significantly suppressed the invasiveness of highly aggressive 253J-BV bladder cancer cells. Moreover, our results demonstrated that BLT2 mediates invasiveness through a signaling pathway dependent on NAD(P)H oxidase (Nox) 1- and Nox4-induced generation of reactive oxygen species (ROS) and subsequent NF-κB stimulation. Metastasis of 253J-BV cells in mice was also dramatically suppressed by inhibition of BLT2 or its signaling. These findings suggest that a BLT2-Nox-ROS-NF-κB cascade plays a critical role in bladder cancer invasion and metastasis.

Original languageEnglish
Pages (from-to)1072-1081
Number of pages10
JournalFree Radical Biology and Medicine
Volume49
Issue number6
DOIs
Publication statusPublished - 2010 Sep

Keywords

  • BLT2
  • Bladder cancer
  • Free radicals
  • Invasion
  • Metastasis
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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