Altered expression of E-cadherin by hepatocyte growth factor and effect on the prognosis of nasopharyngeal carcinoma.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Xie
Li-qiong
LQ
Department of Pathology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Bian
Li-juan
LJ
Li
Zhi
Z
Li
Yang
Y
Li
Zhi-xun
ZX
Li
Bin
B
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
D015820:Cadherins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met