Altered Expression of E-cadherin by Hepatocyte Growth Factor and Effect on the Prognosis of Nasopharyngeal Carcinoma

Abstract

Hepatocyte growth factor (HGF)-related E-cadherin expression and prognosis of patients with nasopharyngeal carcinoma (NPC) are not fully understood. This study investigated HGF-induced altered expression of E-cadherin and the relationship between prognosis and modulation of E-cadherin by HGF in NPC. 135 cases of NPC were collected, and expression of HGF, c-Met, and E-cadherin in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, as well as the follow-up data of patients, was analyzed statistically. The association and alteration of E-cadherin by HGF treatment in NPC cell lines were evaluated by immunocytochemical staining, Western blot, and invasion assay. Both high HGF expression in tumor cells (62.9%, 85/135 cases) and nonmembranous E-cadherin expression (61.5%, 83/135 cases) were significantly associated with advanced clinical stage, lymph node metastasis, and worse prognosis of NPC patients. However, only abnormal E-cadherin expression (P = 0.001) and lymph node metastasis (P = 0.004) emerged as strong independent prognostic factors for overall survival of NPC patients. In vitro, exogenous HGF decreased and internalized E-cadherin expression from cell membrane to cytoplasm, with obvious cellular morphological change. HGF-treated NPC cells exhibited significantly enhanced invasive ability in Matrigel matrix-coated Transwell chamber assay. HGF may contribute to cell invasion in NPC by modulating E-cadherin-mediated cell-cell adhesion through downregulation and internalization of E-cadherin. Altered expression of E-cadherin by HGF is a valuable predictor for prognostic evaluation of NPC patients.