Mechanism of the Lymph Node Metastasis in Human Esophageal Cancer -Epidermal Growth Factor Causes Dysfunction of Cadherin-mediated Cell-cell Adhesion-

Hitoshi Shiozaki, Masatoshi Inoue, Shigeyuki Tamura, Yuuichiro Doki, Takatoshi Kadowaki, Yutaka Kimura, Morito Monden

Department of Surgery 2, Osaka University Medical School

Previous studies found that overexpression of the epidermal growth factor receptor (EGF-R) and reduced expression of E-cadherin and α-caenin were associated with lymph node metastasis of esophageal cancer. In the present study, we examined whether EGF was in part responsible for the dysfunction of cadherin-mediated cell-cell adhesion in the human esophageal cancer cell line TE-2R, which expresses E-cadherin and EGF-R. In the presence of EGF, TE-2R changed its colony formation from compact to sparse. In the cell dissociation assay, EGF strongly facilitated the dissociation of TE-2R cells in a dose-dependent manner. Moreover, EGF enabled the cells to invade an organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its location from the lateral adhesion site to the whole cell surface. Finally, we observed tyrosine phosphorylation of β-catenin induced by EGF. These results suggest that EGF might counteract Ecadherin mediated cell-cell adhesion through phosphorylation of β-catenin and modulate tumor cells to a more aggressive phenotype for lymph node metastasis of esophageal cancer.

Key words
EGF-R, E-cadherio, tyrosin phosphorylation

Reprint requests
Hitoshi Shiozaki Department of Surgery 2, Osaa University Medical School
2-2 Suita, Osaka, 565 JAPAN

Accepted
November 15, 1995

To read the PDF file you will need Abobe Reader installed on your computer.