PMID- 26299331 OWN - NLM STAT- MEDLINE DCOM- 20160719 LR - 20240204 IS - 0219-1032 (Electronic) IS - 1016-8478 (Print) IS - 1016-8478 (Linking) VI - 38 IP - 9 DP - 2015 Sep TI - LPS Up-Regulates ICAM-1 Expression in Breast Cancer Cells by Stimulating a MyD88-BLT2-ERK-Linked Cascade, Which Promotes Adhesion to Monocytes. PG - 821-8 LID - 10.14348/molcells.2015.0174 [doi] AB - 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. FAU - Park, Geun-Soo AU - Park GS AD - School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea. FAU - Kim, Jae-Hong AU - Kim JH AD - School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150821 PL - United States TA - Mol Cells JT - Molecules and cells JID - 9610936 RN - 0 (ICAM1 protein, human) RN - 0 (LTB4R2 protein, human) RN - 0 (Lipopolysaccharides) RN - 0 (MYD88 protein, human) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Receptors, Leukotriene B4) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Breast Neoplasms MH - Cell Adhesion/drug effects MH - Cell Line, Tumor MH - Coculture Techniques MH - Female MH - Humans MH - Intercellular Adhesion Molecule-1/genetics/*metabolism MH - Lipopolysaccharides/*pharmacology MH - MAP Kinase Signaling System MH - Monocytes/immunology/*metabolism MH - Myeloid Differentiation Factor 88/metabolism MH - Receptors, Leukotriene B4/metabolism MH - Up-Regulation PMC - PMC4588726 OTO - NOTNLM OT - BLT2 OT - ICAM-1 OT - LPS OT - MyD88 OT - beast cancer EDAT- 2015/08/25 06:00 MHDA- 2016/07/20 06:00 PMCR- 2015/08/21 CRDT- 2015/08/25 06:00 PHST- 2015/06/16 00:00 [received] PHST- 2015/07/17 00:00 [revised] PHST- 2015/07/17 00:00 [accepted] PHST- 2015/08/25 06:00 [entrez] PHST- 2015/08/25 06:00 [pubmed] PHST- 2016/07/20 06:00 [medline] PHST- 2015/08/21 00:00 [pmc-release] AID - S1016-8478(23)05496-1 [pii] AID - molce-38-9-821 [pii] AID - 10.14348/molcells.2015.0174 [doi] PST - ppublish SO - Mol Cells. 2015 Sep;38(9):821-8. doi: 10.14348/molcells.2015.0174. Epub 2015 Aug 21.