Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells

Geun Soo Park, Jae-Hong Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Inflammation and local inflammatory mediators are inextricably linked to tumor progression through complex pathways in the tumor microenvironment. Lipopolysaccharide (LPS) exposure to tumor cells has been suggested to promote tumor invasiveness and metastasis. However, the detailed signaling mechanism involved has not been elucidated. In this study, we showed that LPS upregulated the expression of leukotriene B4 receptor-2 (BLT2) and the synthesis of BLT2 ligands in MDA-MB-231 and MDA-MB-435 breast cancer cells, thereby promoting invasiveness. BLT2 depletion with siRNA clearly attenuated LPS-induced invasiveness. In addition, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies upstream of BLT2 in LPS-potentiated invasiveness and that this 'MyD88-BLT2' cascade mediates activation of NF-κB and the synthesis of IL-6 and IL-8, which are critical for the invasiveness and aggression of breast cancer cells. LPS-driven metastasis of MDA-MB-231 cells was also markedly suppressed by the inhibition of BLT2. Together, our results demonstrate, for the first time, that LPS potentiates the invasiveness and metastasis of breast cancer cells via a 'MyD88-BLT2'-linked signaling cascade.

Original languageEnglish
Pages (from-to)5749-5759
Number of pages11
JournalOncotarget
Volume6
Issue number8
Publication statusPublished - 2015

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Keywords

  • BLT2
  • IL-6/IL-8
  • Invasiveness
  • LPS
  • MyD88

ASJC Scopus subject areas

  • Oncology

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