Ep-CAM transfection in thymic epithelial cell lines triggers the formationof dynamic actin-rich protrusions involved in the organization of epithelial cell layers

Thymic epithelium is organized in a highly connected three-dimensional netw ork through which thymocytes differentiate. The molecular mechanisms underl ying this organization are still unknown. In thymic medulla, a major site o f tolerance induction, the development of the epithelial cell net is tightl y regulated by the needs of thymocyte selection. These reticulated epitheli al cells express high levels of the Ep-CAM molecule. Using different thymic epithelial cell lines as a model system, we found that transfection of Ep- CAM enhances cell growth and leads to a rapid reorganization of the actin c ytoskeleton by inducing the formation of numerous stress fibers and long ce ll protrusions. Finally, the crosslinking of the extracellular domain of a chimeric CD25ec/Ep-CAMic molecule is sufficient to trigger the formation of protrusions. These results suggest that expression of Ep-CAM might balance the organizing capacity of cadherin molecules and may be participating in the formation of a dynamic stromal cell network in the thymus.