An extracellular/membrane bound S100P pool regulates motility and invasion of human extravillous trophoblast lines and primary cells

Tara Lancaster, Maral Ebrahimzadeh Asl Tabrizi, Mariaelena Repici, Janesh K. Gupta, Stephane Gross

Research output: Contribution to journalArticlepeer-review

Abstract

Whilst S100P has been shown to be a marker for carcinogenesis, we have shown, in non physio-pathological states, that its expression promotes trophoblast motility and invasion but the mechanisms explaining these cellular processes are unknown. Here we identify the presence of S100P in the plasma membrane/cell surface of all trophoblast cells tested, whether lines, primary extravillous (EVT) cells or section tissue samples using either biochemical purification ofplasma membrane material, cell surface protein isolation through biotinylation or microscopy analysis. Using extracellular loss of function studies, through addition of a specific S100P antibody, our work shows that inhibiting the cell surface/membrane-bound or extracellular S100P pools significantly reduces, but importantly only in part, both cell motility and cellular invasion in different trophoblastic cell lines, as well as primary EVTs. Interestingly, this loss in cellular motility/invasion did not result in changes to the overall actin organisation and focal adhesion complexes. These findings shed new light on at least two newly characterized pathways by which S100P promotes trophoblast cellular motility and invasion. One where cellular S100P levels involve the remodelling of focal adhesions whilst another, an extracellular pathway, appears to be focal adhesion independent. Both pathways could lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation.
Original languageEnglish
Article number13081231
Number of pages22
JournalBiomolecules
Volume13
Issue number8
Early online date9 Aug 2023
DOIs
Publication statusPublished - 9 Aug 2023

Bibliographical note

Funding: This work was supported by grants from both the Research Group and Biomedical Sciences Research funding schemes at Aston University and a Life and Health Sciences PhD studentship to M.E.A.T.
Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Keywords

  • S100P
  • placenta
  • cytoskeleton
  • trophoblasts
  • membrane
  • migration
  • invasion

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