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.