CELL-ADHESION TO THE APICAL POLE OF EPITHELIUM - A FUNCTION OF CELL POLARITY

Human uterine epithelium displays a distinct polarized organization wi th apical, lateral, and basal plasma membrane domains. Although non-ad hesive throughout most of the menstrual cycle, epithelial cells allow attachment of trophoblast cells to their apical pole during embryo imp lantation. A recent hypothesis postulates that epithelial cells turn o ff genes for apical-basal polarity and turn on genes for a more mesenc hyme-like phenotype allowing cell-cell interaction with trophoblast. U sing an in vitro assay human uterine cell lines (RL95-2, HEC-1-A, AM3- CA) were selected on the basis of adhesiveness for trophoblast-type ce lls (JAR). Subsequently, uterine cells were examined for epithelium-sp ecific ultrastructure using transmission electron microscopy, and for the expression of E-cadherin, alpha 6-, beta 1-, beta 4-integrin sub-u nits and cytokeratin using immunocytochemistry, confocal laser scannin g microscopy, and surface replication technique. HEC-1-A mono layers a re non-adhesive for JAR cells and appear highly polarized expressing E -cadherin, alpha 6-, beta 1-, beta 4-integrin subunits, and cytokerati n. Both, integrins and E-cadherin, are present at the lateral membrane . RL95-2 monolayers which are adhesive for JAR cells appear nonpolariz ed. Like HEC-1-A cells, RL95-2 cells express E-cadherin, alpha 6-, bet a 1- and beta 4-integrin subunits, and cytokeratin. In contrast to HEC 1-A cells, integrins and E-cadherin are distributed at the entire cel l, surface. AN3-CA monolayers are non-adhesive for JAR cells and appea r nonpolarized. Cells lack epithelial-specific markers such as keratin and E-cadherin. They show only low expression of alpha 6-, beta 1-int egrin subunits and lack beta 4-integrin subunit. Conversely, they expr ess vimentin. Thus, modulation of the epithelial phenotype of uterine cells, i.e. loss of apical-basal polarity, might prepare the apical ce ll pole for cell cell interaction with trophoblast. However, loss of c ell polarity would not lead to enhancement of adhesiveness for trophob last if accompanied by a loss of epithelium specific adhesion molecule s.