Change of E-cadherin by hepatocyte growth factor and effects on the prognosis of hypopharyngeal carcinoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Kim
Chul-Ho
CH
Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.
Kim
Janghee
J
Kahng
Hison
H
Choi
Eun Chang
EC
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D049109:Cell Proliferation; D005260:Female; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D015820:Cadherins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met