PMID- 23475608 OWN - NLM STAT- MEDLINE DCOM- 20140911 LR - 20161125 IS - 1098-2744 (Electronic) IS - 0899-1987 (Linking) VI - 53 IP - 8 DP - 2014 Aug TI - Thromboxane A2 receptor-mediated release of matrix metalloproteinase-1 (MMP-1) induces expression of monocyte chemoattractant protein-1 (MCP-1) by activation of protease-activated receptor 2 (PAR2) in A549 human lung adenocarcinoma cells. PG - 659-66 LID - 10.1002/mc.22020 [doi] AB - Matrix metalloproteinases (MMPs) and monocyte chemoattractant protein-1 (MCP-1, CCL2) are known to be upregulated in many tumors. Their roles in tumor invasion and metastasis are being uncovered. How they are related to each other and involved in tumor progression remains to be determined. Earlier it was reported that I-BOP-initiated activation of thromboxane A2 receptor (TP) induced the release of MMP-1, MMP-3, and MMP-9 from lung cancer A549 cells overexpressing TPalpha (A549-TPalpha). Herein it was found that MMP-1, but not MMP-3 or MMP-9, induced the expression of MCP-1 in A549 cells. Conditioned medium (CM) from I-BOP activated, MMP-1 siRNA pretreated A549-TPalpha cells induced greatly attenuated expression of MCP-1 in A549 cells indicating that MMP-1 in the CM contributed significantly to the expression of MCP-1. MMP-1 was shown to activate protease-activated receptor 2 (PAR2) instead of commonly assumed PAR1 to increase the expression of MCP-1 in A549 cells. This conclusion was reached from the following findings: (1) expression of MCP-1 induced by trypsin, a PAR2 agonist, and also PAR2 agonist peptide, was inhibited by a PAR2 antagonist; (2) expression of MCP-1 induced by MMP-1 and by CM from I-BOP activated A549-TPalpha cells was blocked by a PAR2 antagonist but not by other PAR antagonists; (3) expression of MCP-1 induced by MMP-1 and by CM from I-BOP activated A549-TPalpha cells was attenuated significantly by pretreatment of cells with PAR2-siRNA. These results suggest that PAR2 is a novel MMP-1 target mediating MMP-1-induced signals in A549 lung cancer cells. CI - (c) 2013 Wiley Periodicals, Inc. FAU - Li, Xiuling AU - Li X AD - Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky. FAU - Tai, Hsin-Hsiung AU - Tai HH LA - eng PT - Journal Article DEP - 20130308 PL - United States TA - Mol Carcinog JT - Molecular carcinogenesis JID - 8811105 RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Culture Media, Conditioned) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (Receptor, PAR-2) RN - 0 (Receptors, Thromboxane A2, Prostaglandin H2) 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 - EC 3.4.24.7 (MMP1 protein, human) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Adenocarcinoma/drug therapy/genetics/*metabolism MH - Blotting, Western MH - Bridged Bicyclo Compounds, Heterocyclic/pharmacology MH - Chemokine CCL2/genetics/*metabolism MH - Culture Media, Conditioned/pharmacology MH - Fatty Acids, Unsaturated/pharmacology MH - Humans MH - Lung Neoplasms/drug therapy/genetics/*metabolism MH - Matrix Metalloproteinase 1/genetics/*metabolism MH - RNA, Messenger/genetics MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Receptor, PAR-2/antagonists & inhibitors/genetics/*metabolism MH - Receptors, Thromboxane A2, Prostaglandin H2/antagonists & inhibitors/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Cells, Cultured OTO - NOTNLM OT - matrix metalloproteinases OT - monocyte chemoattractant protein-1 OT - protease-activated receptor 2 OT - thromboxane A2 receptor EDAT- 2013/03/12 06:00 MHDA- 2014/09/12 06:00 CRDT- 2013/03/12 06:00 PHST- 2012/09/06 00:00 [received] PHST- 2013/01/24 00:00 [revised] PHST- 2013/02/04 00:00 [accepted] PHST- 2013/03/12 06:00 [entrez] PHST- 2013/03/12 06:00 [pubmed] PHST- 2014/09/12 06:00 [medline] AID - 10.1002/mc.22020 [doi] PST - ppublish SO - Mol Carcinog. 2014 Aug;53(8):659-66. doi: 10.1002/mc.22020. Epub 2013 Mar 8.