Tissue-specific expression of the relaxed conformation of plasminogen activator inhibitor-2 and low-density lipoprotein receptor-related protein in human term gestational tissues

Dina Tsatas, Mark S. Baker*, Gregory E. Rice

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The relaxed conformation of plasminogen activator inhibitor-2 (PAIr) is formed during inactivation of the matrix-degrading enzyme urokinase plasminogen activator (uPA). The presence of PAIr in tissues, therefore, indicates the in situ inhibition of uPA-mediated proteolysis. In addition, PAIr functions as a ligand for the clearance receptor low-density lipoprotein receptor-related protein (LRP), thereby promoting internalization of receptor-bound uPA-PAIr complexes from the cell surface. The rapid internalization of receptor-bound, inactivated uPA has been suggested to be characteristic of invasive cell phenotypes. The aims of this study were to characterize the immunohistochemical localization of PAir in human term gestational tissues (amnion, choriodecidua, and placenta) and to establish its co-expression with other components of the uPA cascade. The results obtained indicate that PAIr immunoreactivity was exclusively localized to amnion epithelial cells, with only minimal staining in the underlying chorion. PAir immunoreactivity was not detectable in any of the trophoblastic tissues examined (villous and extravillous). The tissue-specific expression of PAIr immunoreactivity was not significantly altered in association with labor onset. uPA and PAI-2 staining was localized predominantly to amnion epithelial cells, underlying chorion, and trophoblast cells of villous and extravillous tissue. Amnion and trophoblasts of extravillous and chorionic tissue showed uPAR immunoreactivity, whereas staining in placenta was absent. Immunoreactive LRP was confined to trophoblasts of the chorion, and the villous and extravillous tissue. For the first time, localization of PAIr at the tissue level has been identified. The data obtained are consistent with the hypothesis that cells of invasive phenotype, although expressing all components of the uPA cascade, do not accumulate immunoreactive PAIr, because it is rapidly internalized from the cell surface. Conversely, cells of noninvasive phenotype will accumulate PAIr immunoreactivity only in the absence of LRP expression. We propose that the presence of PAIr and the absence of LRP at the cell surface are putative markers of noninvasive phenotypes.

Original languageEnglish
Pages (from-to)1593-1602
Number of pages10
JournalJournal of Histochemistry and Cytochemistry
Volume45
Issue number12
Publication statusPublished - Dec 1997
Externally publishedYes

Keywords

  • Cascade
  • Gestational tissue
  • Immunohistochemistry
  • Matrix remodeling
  • Plasminogen activation

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