Changing roles of cadherins and catenins during progression of squamous intraepithelial lesions in the uterine cervix

Uterine cervix represents a convenient model for the study of the gradual t ransformation of normal squamous epithelium via low- to high-grade squamous intraepithelial lesions (SILs), Because SIL, on the basis of the cytokerat ins expressed, are thought to originate from the reserve cells, we analyzed whether SILs also show a reserve cell, phenotype with respect to intercell ular interactions. The changes in expression and subcellular localization o f the components of the adherens junction and desmosomal complexes were inv estigated in normal, metaplastic, and premalignant cervical epithelium, as well as in cell cultures derived from these tissues. The results suggest th at 1) during progression of SILs, E-cadherin is suppressed, with its role i n cell-cell connections diminishing; 2) P-cadherin, in contrast, becomes th e predominant cadherin in high-grade SILs; 3) the level of cellular alpha-c atenin is dramatically decreased in high-grade SILs; 4) the level of beta-c atenin is decreased during progression of SILs, with plakoglobin suggestive ly becoming the predominant catenin mediating connection of cadherins to th e cytoskeleton; 5) the assembly of desmosomes is affected during progressio n of SILs and is accompanied by a dramatically decreased expression for des mogleins and desmoplakins (I, II); and 6) expression of differentiation mar kers (involucrin, CK13) in high-grade SILs seems to be controlled by P-cadh erin as opposed to E-cadherin in the normal tissue counterpart. We conclude that during development of cervical lesions substantial (both quantitative and qualitative) changes occur in cell-cell junctions, making the interact ions of cells in lesions dissimilar from those of reserve cells, basal cell s, or cells of immature squamous metaplasia, despite existing morphological similarity between all of these cell types and cells of high-grade lesions .