The expression and function of cadherin-mediated cell-to-cell adhesion in human embryonal carcinoma cells.
Human embryonal carcinoma (EC) cells typically require high cell densities to maintain their characteristic phenotype; they are generally subject to differentiation when cultured at low cell densities, marked by changes in morphology and expression of the surface antigen, SSEA-1. To test whether cadherin mediated cell-to-cell adhesion may be responsible for maintaining an EC phenotype we ascertained that human EC cells generally express E- and P-cadherins, and are subject to cadherin mediated, Ca2+ dependent aggregation. However, in the NTERA2 human EC cell line, inhibition of cadherin mediated adhesion by culture in low levels of Ca2+ did not result in the changes typically seen under low cell density conditions. Low Ca2+ levels also did not affect the pattern of differentiation in these cells following induction with retinoic acid. Therefore, cadherin-mediated cell adhesion does not appear to play a role in maintaining an EC phenotype. On the other hand, culture at both low cell density and in the absence of Ca2+ did result in changes in the patterns of cadherin expression suggesting a feedback regulatory effect of cell-to-cell adhesion. Further, lithium which inhibits the cytoplasmic kinase GSK3beta and hence influences beta-catenin levels did cause differentiation of NTERA2 cells. However, consideration of the phenotype of the resultant cells suggested that this effect may be because of lithium mimicking activation of a Wnt signalling pathway, rather than an effect on signalling consequent upon cadherin mediated cell to cell adhesion.
Giesberts
A N
AN
Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.
Duran
C
C
Morton
I N
IN
Pigott
C
C
White
S J
SJ
Andrews
P W
PW
D015820:Cadherins / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion; D002452:Cell Count; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D004305:Dose-Response Relationship, Drug; D054278:Embryonal Carcinoma Stem Cells; D005434:Flow Cytometry; D006801:Humans; D008094:Lithium / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D013997:Time Factors; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D008094:Lithium; D002118:Calcium