title: Prostaglandin E2/EP1 signaling pathway enhances intercellular adhesion molecule 1 (ICAM-1) expression and cell motility in oral cancer cells.
abstract: Oral squamous cell carcinoma has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin (PG) synthase, has been implicated in tumor metastasis. However, the effects of COX-2 on human oral cancer cells are largely unknown. We found that overexpression of COX-2 or exogenous PGE(2) increased migration and intercellular adhesion molecule 1 (ICAM)-1 expression in human oral cancer cells. Using pharmacological inhibitors, activators, and genetic inhibition of EP receptors, we discovered that the EP1 receptor, but not other PGE receptors, is involved in PGE(2)-mediated cell migration and ICAM-1 expression. PGE(2)-mediated migration and ICAM-1 up-regulation were attenuated by inhibitors of protein kinase C (PKC)δ, and c-Src. Activation of the PKCδ, c-Src, and AP-1 signaling pathway occurred after PGE(2) treatment. PGE(2)-induced expression of ICAM-1 and migration activity were inhibited by a specific inhibitor, siRNA, and mutants of PKCδ, c-Src, and AP-1. In addition, migration-prone sublines demonstrated that cells with increased migration ability had higher expression of COX-2 and ICAM-1. Taken together, these results indicate that the PGE(2) and EP1 interaction enhanced migration of oral cancer cells through an increase in ICAM-1 production.
authors.affiliation: From the Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.forename: Tsung-Te
authors.initials: TT
authors.lastname: Chung
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.forename: Chih-Hsin
authors.initials: CH
authors.lastname: Tang
mesh_terms: D000081247:CSK Tyrosine-Protein Kinase; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D010120:Oxytocics / Q000378:metabolism / Q000494:pharmacology*; D051745:Protein Kinase C-delta / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases
chemical_list: D010120:Oxytocics; C545635:PTGER1 protein, human; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D018808:Transcription Factor AP-1; D018799:Intercellular Adhesion Molecule-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D051745:Protein Kinase C-delta; D015232:Dinoprostone