Expression of integrin alpha 6 beta 4 in human trophoblast and its loss from extravillous cells

Villous trophoblast from first trimester and term placenta expresses the integrin subunits alpha 6 and beta 4, as monitored by immunohistochemistry. The subunits, which co-distribute in all locations, are present at the basal cell surface where cyto- and syncytiotrophoblast make contact with the villous basement membrane and, in addition, in areas of contact between cytotrophoblast or cyto- and syncytiotrophoblast, but both are absent from the apical syncytial surface. This distribution, which together with other evidence suggests that the two subunits are associated in trophoblast as the heterodimer alpha 6 beta 4, differs from other epithelia in which alpha 6 beta 4 is predominantly basally disposed. Anti-cytokeratin antibodies were used to identify cytotrophoblast columns at the tips of anchoring villi and the migratory interstitial extravillous cytotrophoblast population in the placental bed. Cells in the columns showed a level of expression that diminished with distance from the villous basement membrane, and the alpha 6 and beta 4 subunits were not detected in interstitial cytotrophoblast. In trophoblast of the chorion laeve, both the subunits were expressed in all layers from the pseudobasement membrane to the edge of the parietal decidua, but not in the decidua itself. Integrin alpha 6 beta 4 distribution was also examined in primary cultures of term trophoblast and in the choriocarcinoma cell line BeWo. The alpha 6 and beta 4 subunits were present at or near cell contact areas, where basement membrane components including laminin were also detected. The results suggest that integrin alpha 6 beta 4 plays a role in anchoring trophoblast to basement membrane and its loss may play a role in enabling cells to migrate into the maternal tissue compartment.