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

Thymic epithelium is organized in a highly connected three-dimensional network through which thymocytes differentiate. The molecular mechanisms underlying this organization are still unknown. In thymic medulla, a major site of tolerance induction, the development of the epithelial cell net is tightly regulated by the needs of thymocyte selection. These reticulated epithelial 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 cytoskeleton by inducing the formation of numerous stress fibers and long cell 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.