Hepatogastroenterology

Abstract

BACKGROUND/AIMS: Lysophosphatidic acid (LPA) has diverse biological activities implicated in tumor progression, including increasing cell migration, invasion and metastasis. However, the underlying mechanisms for LPA-induced human hepatocellular carcinoma (HCC) migration and invasion are poorly understood. METHODOLOGY: We sought to determine the promoting effect of LPA on HCC migration, invasion and adhesion by transwell and matrix adhesion assays, respectively. Levels of matrix metalloproteinase, MMP-2 and MMP- 9 from cells were assayed by ELISA and p38 mitogenactivated protein kinase (MAPK) signaling was determined by western blot analysis. RESULTS: In the present study, LPA was found to increase HCC cell migration, invasion and adhesion. In addition, LPA increased MMP-9 expression level and induced activation of the p38 mitogen- activated protein kinase (MAPK) signaling. Furthermore, pharmacological inhibition of p38 MAPK signal pathway with SB203580 significantly attenuated LPA-induced HCC cell migration, invasion, and adhesion and abrogated LPA-induced MMP-9 expression and p38 MAPK phosphorylation. CONCLUSIONS: We demonstrated a mechanism that LPA can activate p38 MAPK signaling, which is required for LPA-induced HCC cell migration, invasion, adhesion and MMP-9 expression, providing a novel biomarker and potential therapeutic target for HCC.