EXPRESSION AND IN-VITRO REGULATION OF INTEGRINS BY NORMAL HUMAN UROTHELIAL CELLS

Integrins are thought to be essential adhesion receptors for the maint enance of tissue histioarchitecture. The purpose of this study was to determine integrin expression patterns in the human stratified transit ional epithelium of the urinary tract (urothelium). In situ expression patterns were compared with in vitro expression, using a normal cell culture model system in which the effects of cell stratification can b e studied independently of differentiation. By immunohistological crit eria, the urothelia of bladder, ureter and renal pelvis expressed alph a 2 beta 1 and alpha 3 beta 1 integrins in all layers at intercellular junctions, and cytoplasmically in the lower strata. By contrast, alph a 6 beta 4 and occasionally alpha v beta 4 were expressed only by basa l cells and localised to the basal lamina. These expression patterns w ere unaltered in specimens where an inflammatory cell infiltrate was p resent. In long-term cultures of normal urothelial cells maintained in a low-Ca(++)serum-free medium, the monolayer cultures expressed alpha 2 beta 1, alpha 3 beta 1 and alpha 5 beta 1 integrins at intercellula r junctions and in cytoplasmic inclusions, whereas alpha 6 beta 4 was distributed in a random pattern over the substratum. Increasing exogen ous Ca(++)concentrations induced cell stratification and desmosome for mation, but not cytodifferentiation. Under these conditions, alpha 6 b eta 4 became cell-, rather than substratum-associated, localising part icularly to filopodia and lamellipodia. Quantitation of integrin expre ssion by flow cytometry confirmed increased surface expression of alph a 6 beta 4 in high Ca(++)media, and also of alpha 3 and alpha 5, but n ot alpha 2, subunits. These results suggest that alpha 2 beta 1 and al pha 3 beta 1 integrins, although differentially regulated, are mainly involved in homotypic cell-cell interactions and the maintenance of a stratified morphology, whereas alpha 6 beta 4 is the principal integri n involved in substratum adhesion.