Prostaglandin E2 promotes migration and adhesion in hepatocellular carcinoma cells

The effect of the expression of cyclooxygenase-2 (COX-2) and prostaglandin E-2 (PGE(2)) 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 PGE(2). Hepatocellular carcinoma (HCC) cells expressed beta 1 and alpha V beta 3 integrins, exhibiting an increase in cell adhesion onto fibronectin and vitronectin. Moreover, addition of PGE(2) increased the beta 1 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 PGE(2), indicating the involvement of multiple pathways in the process. Taken together, these results support the existence of a relationship between COX-2-derived PGE(2) synthesis, and migration and adhesion through an integrin-dependent pathway in HCC cells.