Vascular Endothelial Growth Factor Receptor-1 Activation Mediates Epithelial to Mesenchymal Transition in Hepatocellular Carcinoma Cells

PURPOSE: To explore the molecular mechanism of Vascular endothelial growth factor receptor-1 (VEGFR-1) in invasion and metastasis of hepatocellular carcinoma. METHODS: Reverse transcription polymerase chain reaction was performed to test expression of VEGFR-1 and its ligand VEGF-B19 in four hepatoma carcinoma cell. Fluorescent immunohistochemistry and western blotting were used to test the change of expression of E-cadherin or α-catenin. RESULTS: VEGF-B-treated cells exhibited a change in E-cadherin from an organized, membrane-bound structure to a disorganized state that was dispersed throughout the cytoplasm. The maximal changes in E-cadherin were observed 24 hr after treatment of cells with VEGF-B. α-catenin was observed to translocate to the nucleus from its usual membrane-bound location 24 hr after treatment with either VEGF-B. Expression of the epithelial adhesion molecules E-cadherin was observed to decrease 48 hours after VEGF-B treatment. The nuclear expression of α-catenin was observed to increase 24 hr after treatment with VEGF-B. CONCLUSIONS: VEGFR-1 on tumor cells may contribute to the aggressive behavior of hepatocellular carcinoma cells by inducing epithelial to mesenchymal transition (EMT). Targeting VEGFR-1 and downstream mediators of EMT may provide the foundation for the development of novel therapeutic approaches for this morbid and lethal disease.