HUMAN TROPHOBLAST ADHESION TO MATRIX PROTEINS - INHIBITION AND SIGNAL-TRANSDUCTION

At the time of implantation, the extracellular matrix proteins laminin and fibronectin are abundant in the decidua and are distributed peric ellularly around each individual stromal cell. First trimester human t rophoblast expresses both laminin and fibronectin receptors, specifica lly the alpha(1) beta(1),alpha(5) beta(1),alpha(6) beta(4) and alpha(6 ) beta(4) integrin heterodimers. In this study we have demonstrated th at in-vitro adhesion of first trimester human trophoblast to purified extracellular matrix proteins and to purified decidual stromal cell mo nolayers can be inhibited by monoclonal antibodies directed against ap propriate integrin subunits and by synthetic peptides containing an ar ginine-glycine-aspartic acid sequence. Monoclonal antibodies (mAbs) to the alpha(5) and beta(1) integrin subunits and a synthetic peptide si gnificantly inhibited adhesion to fibronectin. Binding of trophoblast to laminin was blocked with mAbs to the alpha(6) and beta(1) but not a lpha(1) and beta(4) integrin subunits. Similarly, integrin-mediated ad hesion to monolayers of decidual stromal cells could be blocked with m Abs to the alpha(5), alpha(6), beta(1) and beta(4) integrin subunits. Integrin-mediated signal transduction in normal and malignant trophobl ast was investigated by Western blotting. A 115 kDa protein was the ma jor tyrosine phosphorylated protein detected in trophoblast after bind ing to laminin or fibronectin. The profile of tyrosine phosphorylated proteins differed for malignant trophoblast.