S100P enhances the motility and invasion of human trophoblast cell lines

Maral E A Tabrizi,Philip S Rudland,Tara L Lancaster,Athina Georgiadou,Shakil Ahmad,Ankana Ganguly,Stephane R Gross,Jayna J Mistry,Thamir M Ismail,Keqing Wang

doi:10.1038/s41598-018-29852-2

Maral E A Tabrizi, Philip S Rudland + Show 8 more

Open Access

https://doi.org/10.1038/s41598-018-29852-2

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Abstract

S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein’s role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation.

Highlights

Trophoblast invasion of the decidualised endometrium to establish the precursor of the placenta, the first step of implantation, is a tightly regulated process, orchestrated by the continuous cross-talk between foetal and maternal compartments
Reports of occurrence of S100 protein expression from the foetal side have been more infrequent, for example, CaBP-d28k has been reported to be expressed in trophoblast Jeg-3 cells[7] and in vivo[8], whilst S100B, S100A4, S100A6 and S100A8 expression have been observed in trophoblasts[9,10,11,12]
S100P expression has been linked to progression of malignancy of cells originating from numerous tissue sources, such as breast, pancreas and lung[39,40,41,42,43,44] with supporting evidence showing that S100P acts a regulator of cellular invasiveness and motility in multiple human carcinoma cell lines[23,31,32,33]

Summary

Introduction

Trophoblast invasion of the decidualised endometrium to establish the precursor of the placenta, the first step of implantation, is a tightly regulated process, orchestrated by the continuous cross-talk between foetal and maternal compartments. During this stage, one of the prominent factors for proper embryonic development is the successful migration and invasion of extravillous trophoblast cells into the maternal decidua and myometrium. The reciprocal experiment, using the first trimester HTR8/SVneo extravillous trophoblast cell line, in which S100P expression is overexpressed, demonstrates that high levels of S100P correlates with significant increases in motility and invasion. Our data demonstrates a new function for S100P which links its well characterised motility and invasionenhancing properties to a physiological process, that of placental implantation

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