PMID- 23349788 OWN - NLM STAT- MEDLINE DCOM- 20130724 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 1 DP - 2013 TI - Activation of thromboxane A2 receptor (TP) increases the expression of monocyte chemoattractant protein -1 (MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) and recruits macrophages to promote invasion of lung cancer cells. PG - e54073 LID - 10.1371/journal.pone.0054073 [doi] LID - e54073 AB - Thromboxane synthase (TXAS) and thromboxane A(2) receptor (TP), two critical components for thromboxane A(2) (TXA(2)) signaling, have been suggested to be involved in cancer invasion and metastasis. However, the mechanisms by which TXA(2) promotes these processes are still unclear. Here we show that TXA(2) mimetic, I-BOP, induced monocyte chemoattractant protein -1(MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) expression at both mRNA and protein levels in human lung adenocarcinoma A549 cells stably over-expressing TP receptor alpha isoform (A549-TPalpha). The induction of MCP-1 was also found in other lung cancer cells H157 and H460 that express relatively high levels of endogenous TP. Using specific inhibitors of several signaling molecules and promoter/luciferase assay, we identified that transcription factor SP1 mediates I-BOP-induced MCP-1 expression. Furthermore, supernatants from I-BOP-treated A549-TPalpha cells enhanced MCP-1-dependent migration of RAW 264.7 macrophages. Moreover, co-culture of A549 cells with RAW 264.7 macrophages induced expression of MMPs, VEGF and MCP-1 genes, and increased the invasive potential in A549 cells. These findings suggest that TXA(2) may stimulate invasion of cancer cells through MCP-1-mediated macrophage recruitment. FAU - Li, Xiuling AU - Li X AD - Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA. FAU - Tai, Hsin-Hsiung AU - Tai HH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130117 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (Chemokine CCL2) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (Receptors, Thromboxane A2, Prostaglandin H2) RN - 0 (Sp1 Transcription Factor) RN - 0 (Vascular Endothelial Growth Factor A) RN - 124924-85-2 (7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid) RN - 57576-52-0 (Thromboxane A2) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Animals MH - Blotting, Western MH - Bridged Bicyclo Compounds, Heterocyclic/pharmacology MH - Cell Line MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Chemokine CCL2/genetics/*metabolism MH - Coculture Techniques MH - Fatty Acids, Unsaturated/pharmacology MH - Gene Expression/drug effects MH - Humans MH - Lung Neoplasms/genetics/metabolism/pathology MH - Macrophages/cytology/*metabolism MH - Matrix Metalloproteinases/genetics/metabolism MH - Microscopy, Fluorescence MH - Neoplasm Invasiveness MH - Receptors, Thromboxane A2, Prostaglandin H2/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sp1 Transcription Factor/metabolism MH - Thromboxane A2/pharmacology MH - Vascular Endothelial Growth Factor A/genetics/metabolism PMC - PMC3547941 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/01/26 06:00 MHDA- 2013/07/25 06:00 PMCR- 2013/01/17 CRDT- 2013/01/26 06:00 PHST- 2012/05/29 00:00 [received] PHST- 2012/12/06 00:00 [accepted] PHST- 2013/01/26 06:00 [entrez] PHST- 2013/01/26 06:00 [pubmed] PHST- 2013/07/25 06:00 [medline] PHST- 2013/01/17 00:00 [pmc-release] AID - PONE-D-12-15041 [pii] AID - 10.1371/journal.pone.0054073 [doi] PST - ppublish SO - PLoS One. 2013;8(1):e54073. doi: 10.1371/journal.pone.0054073. Epub 2013 Jan 17.