[Mechanism of the lymph node metastasis in human esophageal cancer (epidermal growth factor causes the dysfunction of cadherin-mediated cell-cell adhesion)].
Previous studies reported that the overexpression of the epidermal growth factor receptor (EGF-R) and reduced expression of E-cadherin and alpha-catein were associated with lymph node metastasis of the esophageal cancer. In the present study, we examined that epidermal growth factor (EGF) caused in part the dysfunction of cadherin-mediated cell-cell adhesion using the human esophageal cancer cell line (TE-2R), which expressed 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 in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Finally, we observed tyrosine phosphorylation of beta-catenin induced by EGF. These results might suggest that EGF counteracts E-cadherin mediated cell-cell adhesion through phosphorylation of beta-catenin and modulates tumor cell behaviour to a more aggressive phenotype for lymph node metastasis of the esophageal cancer.
Shiozaki
H
H
Department of Surgery 2, Osaka University Medical School, Japan.
D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000473:pathology*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D004815:Epidermal Growth Factor