Roles of E- and P-cadherin in the human skin

Abstract

The Ca2+‐dependent cell‐cell adhesion molecules, termed cadherins, are subdivided into several subclasses. E (epithelial)‐ and P (placental)‐cadherins are involved in the selective adhesion of epidermal cells. E‐cadherin is expressed on the cell surfaces of all epidermal layers and P‐cadherin is expressed only on the surfaces of basal cells. Ultrastructural studies have shown that E‐cadherin is distributed on the plasma membranes of keratinocytes with a condensation in the intercellular space of the desmosomes. During human skin development P‐cadherin expression is spatiotemporally controlled and closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine ducts. In human skin diseases E‐cadherin expression is markedly reduced on the acantholytic cells of tissues in pemphigus and Darier's disease. Cell adhesion molecules are now considered to play a significant role in the cellular connections of cancer and metastatic cells. Reduced expression of E‐cadherin on invasive neoplastic cells has been demonstrated for cancers of the stomach, liver, breast, and several other organs. This reduced or unstable expression of E‐ and P‐cadherin is observed in squamous cell carcinoma, malignant melanoma, and Paget's disease, but cadherin expression is conserved in basal cell carcinoma. Keratinocytes cultured in high calcium produce much more intense immunofluorescence of intercellular E‐ and P‐cadherin than those cells grown in low calcium. E‐cadherins on the plasma membrane of the keratinocytes are shifted to desmosomes under physiological conditions, and therein may express an adhesion function in association with other desmosomal cadherins. Soluble E‐cadherins in sera are elevated in various skin diseases including bullous pemphigoid, pemphigus vulgaris, and psoriasis, but not in patients with burns. Markedly high levels in soluble E‐cadherin are demonstrated in patients with metastatic cancers. Microsc. Res. Tech. 38:343–352, 1997. © 1997 Wiley‐Liss, Inc.

T-Cadherin Negatively Regulates the Proliferation of Cutaneous Squamous Carcinoma Cells

“…It is reported that the expressions of E-and P-cadherin are reduced in SCC, melanoma, and Paget's disease and reduction of cadherin expression is considered to be related to the detachment of carcinoma cells from the tumor mass (Shirahama et al, 1996;Furukawa, 1997). The contribution of T-cadherin to keratinocyte cell-cell adhesion, however, is not yet known.…”

Human Fat2 is localized at immature adherens junctions in epidermal keratinocytes

“…1c), indicating that there was no cross-reactivity of the antibody with Fat1. Therefore, we concluded that human keratinocytes express Fat2, in addition to various cadherin molecules such as E-, P-and T-cadherins [6,7].…”

“…Amplification was carried out with 30 cycles. Fat2 mRNA was clearly expressed in NHEK cells and human cutaneous SCC cell line HSC-1 cells [7], but not in melanoma cell line A375 cells, normal human epidermal melanocytes or normal human dermal fibroblasts (Fig. 1a).…”

The Calcium-Sensing Receptor-Dependent Regulation of Cell–Cell Adhesion and Keratinocyte Differentiation Requires Rho and Filamin A

“…Raising the Ca 2+ o concentration ([Ca 2+ ] o ) above 0.1 mM induces an increase in intracellular free Ca 2+ concentration ([Ca 2+ ] i ) (Pillai and Bikle, 1991) and intercellular adhesion (Hennings and Holbrook, 1983). E-cadherin-mediated cell-cell adhesion plays a key role in maintaining the tissue integrity and differentiation of epidermal keratinocytes (Furukawa et al , 1997; Tinkle et al , 2004; Young et al , 2003). Raising [Ca 2+ ] o stimulates the binding of E-cadherin to its counterpart on the surface of neighboring cells, and its interactions with β- (or γ-), α-, and p120-catenins to form the core structure of adherens junctions (AJ) (Perez-Moreno et al , 2003; Pokutta and Weis, 2007).…”