ROLES OF E-CADHERIN AND P-CADHERIN IN THE HUMAN SKIN

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 a nd P-cadherin is expressed only on the surfaces of basal cells. Ultras tructural studies have shown that E-cadherin is distributed on the pla sma membranes of keratinocytes with a condensation in the intercellula r space of the desmosomes. During human skin development P-cadherin ex pression is spatiotemporally controlled and closely related to the seg regation of basal layers as well as to the arrangement of epidermal ce lls into eccrine ducts. In human skin diseases E-cadherin expression i s markedly reduced on the acantholytic cells of tissues in pemphigus a nd Darier's disease. Cell adhesion molecules are now considered to pla y a significant role in the cellular connections of cancer and metasta tic cells. Reduced expression of E-cadherin on invasive neoplastic cel ls has been demonstrated for cancers of the stomach, liver, breast, an d 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 cel l carcinoma. Keratinocytes cultured in high calcium produce much more intense immunofluorescence of intercellular E-and P-cadherin than thos e cells grown in low calcium. E-cadherins on the plasma membrane of th e keratinocytes are shifted to desmosomes under physiological conditio ns, and therein may express an adhesion function in association with o ther desmosomal cadherins. Soluble E-cadherins in sera are elevated in various skin diseases including bullous pemphigoid, pemphigus vulgari s, and psoriasis, but not in patients with burns. Markedly high levels in soluble E-cadherin are demonstrated in patients with metastatic ca ncers. (C) 1997 Wiley-Liss. Inc.