Change of E-Cadherin by Hepatocyte Growth Factor and Effects on the Prognosis of Hypopharyngeal Carcinoma

Abstract

Hepatocyte growth factor (HGF) is known to induce scattering in various epithelial cells, and E-cadherin plays important roles in the maintenance of cell-cell adhesion. However, the mechanisms surrounding these actions are not fully understood. Therefore, we examined how HGF affects the expression and distribution of E-cadherin. In addition, we observed the relationship between prognosis and modulation of E-cadherin by HGF in hypopharyngeal carcinoma. Tumor tissues from 66 patients with hypopharyngeal squamous cell carcinoma were evaluated for the expression of HGF, its receptor (c-Met), and E-cadherin. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot test were performed on hypopharyngeal cancer tissues. The association and changes of E-cadherin with HGF treatment in a hypopharyngeal cancer cell line were investigated by RT-PCR, Western blot analysis, inhibition assay, immunofluorescence staining, and invasion assay. E-cadherin expression was found in 87.9% of squamous cell carcinomas; these could be further classified as membranous type (46.9%) or nonmembranous type (53.1%). The expression of HGF in tumors with nonmembranous type E-cadherin expression was far higher than in tumors with membranous expression. Nonmembranous type E-cadherin expression correlated significantly with lymph node metastasis, distant metastasis, and recurrence (P < .05). HGF decreased the expression of E-cadherin and induced the translocation of E-cadherin to the cytoplasm. HGF and E-cadherin neutralizing antibody stimulated dispersion, and HGF significantly enhanced the invasion of hypopharyngeal cancer cells in a dose-dependent manner (P < .05). These results suggest that HGF can modulate the expression and intracellular localization of E-cadherin in hypopharyngeal cancer cells. In addition, these results indicate that changes in E-cadherin by HGF can affect the prognosis of hypopharyngeal carcinoma.