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 pericellularly around each individual stromal cell. First trimester human trophoblast expresses both laminin and fibronectin receptors, specifically the alpha 1 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrin heterodimers. In this study we have demonstrated that in-vitro adhesion of first trimester human trophoblast to purified extracellular matrix proteins and to purified decidual stromal cell monolayers can be inhibited by monoclonal antibodies directed against appropriate integrin subunits and by synthetic peptides containing an arginine-glycine-aspartic acid sequence. Monoclonal antibodies (mAbs) to the alpha 5 and beta 1 integrin subunits and a synthetic peptide significantly inhibited adhesion to fibronectin. Binding of trophoblast to laminin was blocked with mAbs to the alpha 6 and beta 1 but not alpha 1 and beta 4 integrin subunits. Similarly, integrin-mediated adhesion to monolayers of decidual stromal cells could be blocked with mAbs to the alpha 5, alpha 6, beta 1 and beta 4 integrin subunits. Integrin-mediated signal transduction in normal and malignant trophoblast was investigated by Western blotting. A 115 kDa protein was the major tyrosine phosphorylated protein detected in trophoblast after binding to laminin or fibronectin. The profile of tyrosine phosphorylated proteins differed for malignant trophoblast.
Department of Pathology, University of Cambridge, UK.
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Burrows
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King
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Smith
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Loke
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion; D002822:Choriocarcinoma; D003656:Decidua / Q000166:cytology; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D011247:Pregnancy; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology; D014327:Trophoblasts / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D016023:Integrins; D007797:Laminin; D010455:Peptides