Journal Article

Prostaglandin E<sub>2</sub> promotes migration and adhesion in hepatocellular carcinoma cells

Rafael Mayoral, Amalia Fernández-Martínez, Lisardo Boscá and Paloma Martín-Sanz

in Carcinogenesis

Volume 26, issue 4, pages 753-761
Published in print April 2005 | ISSN: 0143-3334
Published online April 2005 | e-ISSN: 1460-2180 | DOI:

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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 β1 and αVβ3 integrins, exhibiting an increase in cell adhesion onto fibronectin and vitronectin. Moreover, addition of PGE2 increased the β1 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.

Keywords: COX, cyclooxygenase (COX-1, COX-2); EGFR, epidermal growth factor receptor; FAK, focal adhesion kinase; HBx, hepatitis B virus X protein; HCC, hepatocellular carcinoma; HGF, hepatocyte growth factor; HUVEC, human umbilical vein endothelial cells; MAPK, mitogen-activated protein kinase; MEK/ERK, mitogen activated protein kinase/extracellular signal-regulated kinase; MMPs, matrix metalloproteinases; NSAIDs, non-steroidal anti-inflammatory drugs; PG, prostaglandin (PGE2, PGJ2); PK, protein kinase (PKA, PKB); VEGF, vascular endothelial growth factor

Journal Article.  5689 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics