An Extracellular/Membrane-Bound S100P Pool Regulates Motility and Invasion of Human Extravillous Trophoblast Lines and Primary Cells

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 of plasma 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.

S100 Proteins—Intracellular and Extracellular Function in Norm and Pathology

“…Still others look for possible correlations between the level of particular S100 proteins and various pathologies (e.g., 8, 11, and 12) in order to establish them as disease markers or provide comprehensive reviews on S100 protein function in norm and pathology (e.g., 7, 14, and 15). 1) and extravillous trophoblast motility and invasion during pregnancy (10) and reveal two independent mechanisms of S100P action. While the intracellular protein enhances cell motility through interaction with myosin IIA and modulation of the focal adhesion pathway, the extracellular, membrane-bound protein acts by a yet unknown mechanism that does not involve changes in focal adhesion.…”

“…Ismail et al, 2021;Lancaster et al, 2023) explore the role of the S100P protein in cell motility in the context of cancer metastasis (…”