Modulation of E-cadherin by hepatocyte growth factor induces aggressiveness of gastric carcinoma.
OBJECTIVE
Hepatocyte growth factor (HGF) is well known as a scatter factor because it can disperse cells. E-cadherin is a protein that plays a main role in the establishment of cell-cell adhesion. This study focused on the role of HGF on the expression and distribution of E-cadherin. Furthermore, we found induction of aggressiveness of gastric carcinoma by modulation of E-cadherin by HGF.


METHODS
Tumor tissues from 50 patients with gastric carcinoma were evaluated for the expression of HGF, its receptor c-Met, and E-cadherin. Western blot analysis and invasion assay were performed to confirm the role of HGF on the modulation of E-cadherin using human gastric cancer cell lines.


RESULTS
Seventy-eight percent of the gastric carcinoma tissues showed overexpression of c-Met. E-cadherin expression was found in 86%, which could be further classified as membranous type (52%) or nonmembranous type (48%). The levels of HGF in tumor tissues increased significantly according to the tumor progression. The levels of HGF in tumors with nonmembranous type E-cadherin expression were significantly higher than those in tumors with membranous expression. A striking morphologic change from epithelial shape to fibroblastic shape was observed in SNU-16 cells after 3 days' exposure to HGF, accompanied by down-regulation of functional E-cadherin in the membrane. Treatment of the cells with HGF induced significant invasion into the matrigel.


CONCLUSIONS
We can conclude that HGF can modulate the expression of E-cadherin in gastric carcinoma, which was accompanied by more aggressive phenotype.
Han
Sang-Uk
SU
Department of Surgery, School of Medicine, Ajou University, Suwon, Korea. hansu@ajou.ac.kr
Lee
Hwa-Young
HY
Lee
Jae-Ho
JH
Kim
Wook-Hwan
WH
Nam
Hyunja
H
Kim
Hong
H
Cho
Yong-Kwan
YK
Kim
Myung-Wook
MW
Lee
Kuhn Uk
KU
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D001707:Biopsy, Needle; D015153:Blotting, Western; D015820:Cadherins / Q000187:drug effects / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation; D015331:Cohort Studies; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D015820:Cadherins; D017228:Hepatocyte Growth Factor