Human trophoblast adhesion to matrix proteins: inhibition and signal transduction

At the time of implantation, the extracellular matrix proteinslaminin and fibronectin are abundant in the decidua and aredistributed pericellularly around each individual stromal cell.First trimester human trophoblast expresses both laminin andfibronectin receptors, specifically the ₁ß_{1 5}ß₁₆ß₁ and ₆ß₄ integrin heterodimers. In thisstudy we have demonstrated that in-vitro adhesion of first trimesterhuman trophoblast to purified extracellular matrix proteinsand to purified decidual stromal cell monolayers can be inhibitedby monoclonal antibodies directed against appropriate integrinsubunits and by synthetic peptides containing an arginine-glycine-asparticacid sequence. Monoclonal antibodies (mAbs) to the ₅ and ß₁integrin subunits and a synthetic peptide significantly inhibitedadhesion to fibronectin. Binding of trophoblast to laminin wasblocked with mAbs to the ₆ and ß₁ but not ₁ and ß₄integrinsubunits. Similarly, integrin-mediated adhesion to monolayersof decidual stromal cells could be blocked with mAbs to the₅, ₆, ß₆ and ß₄ integrin subunits. Integrin-mediatedsignal transduction in normal and malignant trophoblast wasinvestigated by Western blotting. A 115 kDa protein was themajor tyrosine phosphorylated protein detected in trophoblastafter binding to laminin or fibronectin. The profile of tyrosinephosphorylated proteins differed for malignant trophoblast. integrins/matrix/signal transduction/trophoblast