Modulation of E-Cadherin by Hepatocyte Growth Factor Induces Aggressiveness of Gastric Carcinoma

In Brief Objective: Hepatocyte growth factor (HGF) is well known as a scatter factor because it can disperse cells. E-cadherin is a protein that plays a main role in the establishment of cell-cell adhesion. This study focused on the role of HGF on the expression and distribution of E-cadherin. Furthermore, we found induction of aggressiveness of gastric carcinoma by modulation of E-cadherin by HGF. Materials and Methods: Tumor tissues from 50 patients with gastric carcinoma were evaluated for the expression of HGF, its receptor c-Met, and E-cadherin. Western blot analysis and invasion assay were performed to confirm the role of HGF on the modulation of E-cadherin using human gastric cancer cell lines. Results: Seventy-eight percent of the gastric carcinoma tissues showed overexpression of c-Met. E-cadherin expression was found in 86%, which could be further classified as membranous type (52%) or nonmembranous type (48%). The levels of HGF in tumor tissues increased significantly according to the tumor progression. The levels of HGF in tumors with nonmembranous type E-cadherin expression were significantly higher than those in tumors with membranous expression. A striking morphologic change from epithelial shape to fibroblastic shape was observed in SNU-16 cells after 3 days' exposure to HGF, accompanied by down-regulation of functional E-cadherin in the membrane. Treatment of the cells with HGF induced significant invasion into the matrigel. Conclusion: We can conclude that HGF can modulate the expression of E-cadherin in gastric carcinoma, which was accompanied by more aggressive phenotype. The levels of hepatocyte growth factor (HGF) in gastric cancer tissues increased significantly according to the tumor progression and well correlated with the expression of E-cadherin. After treatment with HGF, a more invasive morphologic change was observed in gastric cancer cells, accompanied by down-regulation of functional E-cadherin in the membrane, and invasion into the matrigel. Thus, we suggest that HGF can modulate the expression of E-cadherin in gastric carcinoma.