S100P enhances the motility and invasion of human trophoblast cell lines

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.

A Promising Novel Biomarker For Embryogenesis and Carcinogenesis: S100P Protein

“…The "p" in the name reflects the location of its first isolation, the placenta. Expression of the S100P protein is 90-to 200-fold higher in the placenta than in any other organ [22,23,20]. As might be expected, it is predominantly expressed in the early stages of gestation during placental formation, and this high level of expression continues through the first trimester of pregnancy/ It is reduced by 50% during the second and third trimesters of gestation [22,24].…”

“…Expression of the S100P protein is 90-to 200-fold higher in the placenta than in any other organ [22,23,20]. As might be expected, it is predominantly expressed in the early stages of gestation during placental formation, and this high level of expression continues through the first trimester of pregnancy/ It is reduced by 50% during the second and third trimesters of gestation [22,24]. S100P has been clearly demonstrated to be an important regulator of trophoblast invasion during placentation [22,[24][25][26].…”

“…As might be expected, it is predominantly expressed in the early stages of gestation during placental formation, and this high level of expression continues through the first trimester of pregnancy/ It is reduced by 50% during the second and third trimesters of gestation [22,24]. S100P has been clearly demonstrated to be an important regulator of trophoblast invasion during placentation [22,[24][25][26]. Interestingly, it was suspected that S100P was more dramatically related to cell invasion than cell migration.…”

Circulating RNA Transcriptome of Pregnant Women with TSH Just Above the Trimester-Specific Reference and its Correlation with the Hypertensive Phenotype

“…In a study by Tabrizi M. E. A. et al and Yue X. et al, it was found that S100P and FGF13 may act as regulators of trophoblastic invasion during the placentation period 33,34 . Incomplete invasion of trophoblasts results, for example, in a decrease of uteroplacental blood flow, a condition usually associated with preeclampsia 33 .…”

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

“…Furthermore, 13 novel upregulated genes (10-13 fold) including Esm1, Slfn4, Usp18 and Grem1 and 4 downregulated genes (4-7 fold), including S100g, Pcp4, Col6a4, and Trpc3 were identified in the pregnant UA. While many of these genes were associated with gestational pathologies [34][35][36][37][38][39], the differential expression of these genes in healthy pregnancy relative to non-pregnancy suggests that these genes may have a unique role in gestational uterine vascular adaptations.…”