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Molecular Human Reproduction Vol. 1, NUMBER 2 pp. 74-84, 1995
© European Society of Human Reproduction and Embryology 1995

research-article

Tumour necrosis factor-{alpha}-mediated dyscohesion of epithelial cells is associated with disordered expression of cadherin/ß-catenin and disassembly of actin filaments

S. Tabibzadeh1,2, Q.F. Kong, S. Kapur, P.G. Satyaswaroop3 and K. Aktories4

1Department of Pathology, University of South Florida Health Sciences Center and Moffitt Cancer Center Tampa, FL, USA 3Department of Obstetrics and Gynecology, Hershey Medical Center Hershey, PA, USA 4Institut f{diaeresis}r Pharmacologie und Toxicologie, Der Universität des Saarlandes 66421 Hamburg, Germany

To whom correspondence should be addressed at: 2To whom correspondence should be addressed at: Department of Pathology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA

Tumour necrosis factor (TNF)-{alpha} induced, in a time- and dose-dependent fashion, dyscohesion (cell-cell dissociation) of the endometrial epithelial cells. TNF-{alpha} impaired the ability of cells to aggregate and to attain compaction. The cell-cell adherent junction is a specialized region of the plasma membrane where cadherin molecules act as adhesion molecules and actin filaments are densely associated with the plasma membrane through a well-developed plasmalemmal undercoat. Dyscohesion induced by TNF-{alpha} was associated with the disordered expression of cadherin/ß-catenin at the sites of cell-cell contact. In addition, within the time-frame that dyscohesion was induced, TNF-{alpha} down-regulated the expression of actin mRNA only at 100 ng/ml without modulating the overall amount of actin protein, its ß-isoform or the amount of ribosylated actin. However, TNF-{alpha}-mediated dyscohesion of epithelial cells was associated with loss of plasmalemmal undercoat as well as intracytoplasmic aggregates of F-actin and a simultaneous increase in G-actin. The effect of cytochalasin-B, which disrupts actin filaments on cell-cell binding, was less pronounced than the effect of TNF-{alpha}, suggesting that the effect of this cytokine on dyscohesion is not solely dependent on the disassembly of actin filaments. These findings show that the induction of disordered expression of adhesion molecules, as well as disassembly of actin filaments, are implicated in the dyscohesion induced by TNF-{alpha}.

actin/cell adhesion/cytochalasin/epithelial cells/TNF-{alpha}


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