Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells.
The effect of the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis on cell migration, the secretion of matrix metalloproteinases (MMPs) and the adhesion of human hepatoma cell lines has been investigated. A close correlation was observed between the expression of COX-2 under basal conditions and the secretion of MMP-2 and MMP-9. Cell migration in HuH-7 cells, which express high constitutive levels of COX-2 was significantly inhibited by selective inhibitors of COX-2 and enhanced by exogenous addition of PGE2. Hepatocellular carcinoma (HCC) cells expressed beta1 and alphaV beta3 integrins, exhibiting an increase in cell adhesion onto fibronectin and vitronectin. Moreover, addition of PGE2 increased the beta1 integrin levels and adhesion on vitronectin in HuH-7 cells. Inhibitors of MEK/ERK, p38 MAPK, protein kinases A and C impaired the migration of HuH-7 cells induced by PGE2, indicating the involvement of multiple pathways in the process. Taken together, these results support the existence of a relationship between COX-2-derived PGE2 synthesis, and migration and adhesion through an integrin-dependent pathway in HCC cells.
Mayoral
Rafael
R
Instituto de Bioquímica, Centro Mixto CSIC-UCM and Centro Nacional de Investigaciones Cardiovasculares, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Fernández-Martínez
Amalia
A
Boscá
Lisardo
L
Martín-Sanz
Paloma
P
D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D039302:Integrin alphaVbeta3; D016023:Integrins; D008565:Membrane Proteins; D019030:Receptors, Vitronectin; C094340:integrin alphavbeta1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone