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

Authors
Kim, CH; Kim, J; Kahng, H; Choi, EC
Citation
Annals of surgical oncology, 14(5):1565-1574, 2007
Journal Title
Annals of surgical oncology
ISSN
1068-92651534-4681
Abstract
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.
MeSH terms
Adenocarcinoma/metabolismAdenocarcinoma/secondaryAdenocarcinoma/surgeryAdultAgedBlotting, WesternCadherins/geneticsCadherins/metabolism*Carcinoma, Squamous Cell/metabolismCarcinoma, Squamous Cell/secondaryCarcinoma, Squamous Cell/surgeryCell ProliferationFemaleHepatocyte Growth Factor/geneticsHepatocyte Growth Factor/pharmacology*HumansHypopharyngeal Neoplasms/metabolism*Hypopharyngeal Neoplasms/pathologyHypopharyngeal Neoplasms/surgeryLymphatic Metastasis/pathologyMaleMiddle AgedNeoplasm Invasiveness/pathologyNeoplasm Recurrence, Local/metabolism*Neoplasm Recurrence, Local/pathologyNeoplasm Recurrence, Local/surgeryNeoplasm StagingPrognosisProto-Oncogene Proteins c-met/geneticsProto-Oncogene Proteins c-met/metabolismRNA, Messenger/geneticsRNA, Messenger/metabolismRNA, Neoplasm/geneticsRNA, Neoplasm/metabolismReverse Transcriptase Polymerase Chain ReactionTumor Cells, CulturedTumor Markers, Biological/geneticsTumor Markers, Biological/metabolism*
DOI
10.1245/s10434-006-9320-5
PMID
17294073
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
AJOU Authors
김, 철호김, 장희
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