title: Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells.
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.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Geun-Soo
authors.initials: GS
authors.lastname: Park
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D022423:Myeloid Cells / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D018102:Receptors, Leukotriene B4 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C485878:LTB4R2 protein, human; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D018102:Receptors, Leukotriene B4
keywords: BLT2; IL-6/IL-8; LPS; MyD88; invasiveness