title: LPS Up-Regulates ICAM-1 Expression in Breast Cancer Cells by Stimulating a MyD88-BLT2-ERK-Linked Cascade, Which Promotes Adhesion to Monocytes.
abstract: Monocytes are the major inflammatory cells that infiltrate most solid tumors in humans. The interaction of tumor cells with infiltrating monocytes and their adhesion to these monocytes play a significant role in altering the tumor to become more aggressive. Recently, exposure to lipopolysaccharide (LPS) was suggested to promote cancer cell adhesion to monocytes; however, little is known about the details of the signaling mechanism involved in this process. In this study, we found that LPS up-regulates ICAM-1 expression in MDA-MB-231 breast cancer cells, which facilitates their adhesion to THP-1 monocytes. In addition, we analyzed the signaling mechanism underlying the up-regulation of ICAM-1 and found that the siRNA-mediated depletion of BLT2 markedly suppressed the LPS-induced expression of ICAM-1 in MDA-MB-231 cells and the subsequent adhesion of these cells to THP-1 monocytes. Moreover, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies downstream of LPS/TLR4 and upstream of BLT2 and that this 'MyD88-BLT2' cascade mediates ERK activation and subsequent ICAM-1 expression, which is critical for the adhesion of MDA-MB-231 cells to THP-1 monocytes. Taken together, our results demonstrate for the first time that LPS up-regulates ICAM-1 expression in breast cancer cells via a MyD88-BLT2-ERK-linked signaling cascade, leading to the increased adhesion of breast cancer cells to monocytes.
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors: Geun-Soo
authors: GS
authors: Park
authors: School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.
authors: Jae-Hong
authors: JH
authors: Kim
mesh_terms: D001943:Breast Neoplasms; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D018102:Receptors, Leukotriene B4 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C573420:ICAM1 protein, human; C485878:LTB4R2 protein, human; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D018102:Receptors, Leukotriene B4; D018799:Intercellular Adhesion Molecule-1
keywords: BLT2; ICAM-1; LPS; MyD88; beast cancer