Correlation between E-cadherin expression and invasiveness in vitro in a human esophageal cancer cell line.
E-cadherin, a member of the cadherin family, plays a major role in cell-cell adhesion of normal epithelium. Recent studies have shown that reduction or loss of E-cadherin expression in carcinomas have some relationship with their clinicopathological manifestation including invasion and metastasis. In the present study, we have established cell clones with different E-cadherin expression from human esophageal cancer, TE-2, and examined their adhesive capacity and invasiveness in vitro. Cell clones with positive E-cadherin expression [ECD(+) cells] were round and formed cobblestone colonies, while cell clones negative for E-cadherin [ECD(-) cells] had spindle shapes and formed dispersed colonies. ECD(+) cells showed higher adhesive capacity than ECD(-) cells, in both an aggregation assay with gyratory shaking culture and a dissociation assay of cells passing through the micropore membrane. Monoclonal antibody against human E-cadherin (HECD1) effectively diminished the mutual adhesion of ECD(+) cells but did not affect that of ECD(-) cells. Tumor invasiveness was evaluated with organotypic raft culture which is a coculture system consisting of two layers, a collagen gel layer containing fibroblasts and overlying reconstituted stratified squamous epithelium. ECD(+) cells formed complete stratified epithelium, but ECD(-) cells did not. ECD(+) cells did not invade the collagen/fibroblast gel, but ECD(-) cells did. Furthermore, ECD(+) cells showed invasion when an antibody against E-cadherin was used. Thus, loss or dysfunction of E-cadherin diminishes intercellular adhesion and results in the acquisition of invasive capacity in the cell line we examined.
Doki
Y
Y
Department of Surgery II, Osaka University Medical School, Japan.
Shiozaki
H
H
Tahara
H
H
Inoue
M
M
Oka
H
H
Iihara
K
K
Kadowaki
T
T
Takeichi
M
M
Mori
T
T
D000199:Actins / Q000032:analysis; D015820:Cadherins / Q000378:metabolism*; D002449:Cell Aggregation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured
D000199:Actins; D015820:Cadherins