scholarly journals Human Chorionic Gonadotropin Stimulates Trophoblast Invasion through Extracellularly Regulated Kinase and AKT Signaling

Endocrinology ◽  
2007 ◽  
Vol 149 (3) ◽  
pp. 979-987 ◽  
Author(s):  
Johanna Prast ◽  
Leila Saleh ◽  
Heinrich Husslein ◽  
Stefan Sonderegger ◽  
Hanns Helmer ◽  
...  
Keyword(s):  
Western Blot ◽  
Chorionic Gonadotropin ◽  
First Trimester ◽  
Akt Signaling ◽  
Trophoblast Cell ◽  
Model Systems ◽  
Trophoblast Invasion ◽  
Invasion And Migration ◽  
Explant Cultures ◽  
And Migration

Chorionic gonadotropin (CG) is indispensable for human pregnancy because it controls implantation, decidualization, and placental development. However, its particular role in the differentiation process of invasive trophoblasts has not been fully unraveled. Here we demonstrate that the hormone promotes trophoblast invasion and migration in different trophoblast model systems. RT-PCR and Western blot analyses revealed expression of the LH/CG receptor in trophoblast cell lines and different trophoblast primary cultures. In vitro, CG increased migration and invasion of trophoblastic SGHPL-5 cells through uncoated and Matrigel-coated transwells, respectively. The hormone also increased migration of first-trimester villous explant cultures on collagen I. Proliferation of the trophoblast cell line and villous explant cultures measured by cumulative cell numbers and in situ 5-bromo-2′-deoxyuridine labeling, respectively, was unaffected by CG. Addition of the hormone activated ERK-1/2 and AKT in SGHPL-5 cells and pure, extravillous trophoblasts. Inhibition of MAPK kinase/ERK and phosphatidylinositide 3-kinase/AKT blocked phosphorylation of the kinases and attenuated CG-dependent invasion of SGHPL-5 cells. Similarly, the inhibitors decreased hormone-stimulated migration in villous explant cultures. Western blot analyses and gelatin zymography suggested that CG increased matrix metalloproteinase (MMP)-2 protein levels and activity in both culture systems. Inhibition of ERK or AKT diminished CG-induced MMP-2 expression. In summary, the data demonstrate that CG promotes trophoblast invasion and migration through activation of ERK and AKT signaling involving their downstream effector MMP-2. Because the increase of CG during the first trimester of pregnancy correlates with rising trophoblast motility, the hormone could be a critical regulator of the early invasion process.

Preeclampsia and ox-LDL modify the expression of autophagy markers in placenta and first trimester trophoblast cell line impairing trophoblast invasion and migration.

Placenta ◽  
2019 ◽  
Vol 83 ◽  
pp. e104-e105
Author(s):  
Lorena Carvajal ◽  
Claudette Cantin ◽  
Bárbara Fuenzalida ◽  
Susana Contreras-Duarte ◽  
Jaime Gutierrez ◽  
...  
Keyword(s):  
Cell Line ◽  
First Trimester ◽  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Invasion And Migration ◽  
And Migration ◽  
Trophoblast Cell Line

scholarly journals The Cytokine Gene CXCL14 Restricts Human Trophoblast Cell Invasion by Suppressing Gelatinase Activity

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5596-5605 ◽  
Author(s):  
HaiBin Kuang ◽  
Qi Chen ◽  
Ying Zhang ◽  
Li Zhang ◽  
HongYing Peng ◽  
...  
Keyword(s):  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Gelatinase Activity ◽  
Invasion And Migration ◽  
Human Pregnancy ◽  
Decidual Cells ◽  
And Migration ◽  
Maternal Fetal Interface

Abstract Well-controlled trophoblast invasion into uterine decidua is a critical process for the normal development of placenta, which is tightly regulated by various factors produced within the trophoblast-endometrial microenvironment. CXCL14 is involved in tumor growth and metastasis, and its expression in placenta is temporally regulated during pregnancy. However, the role of CXCL14 in trophoblast function during human pregnancy is not clear. In this study, by using RT-PCR through human pregnancy, we found that CXCL14 was selectively expressed at early but not late pregnancy. Immunostaining revealed that CXCL14 proteins were strongly expressed in villous cytotrophoblasts and moderately in decidualized stromal cells but very weakly in syncytiotrophoblasts and extravillous trophoblasts. The effect of CXCL14 on trophoblast invasion were examined by using human villous explants cultured on Matrigel and further proved by invasion and migration assay of primary trophoblast cells and trophoblast cell line HTR-8/SVneo. Our data showed that CXCL14 significantly inhibited outgrowth of villous explant in vitro; this effect is due to suppression of trophoblast invasion and migration through regulating matrix metalloproteinases activities, whereas the trophoblast proliferation was not affected. Moreover, because a receptor for CXCL14 has not been identified, we performed further cell-specific CXCL14 binding activities with regard to different cell types within the maternal-fetal interface. Our data revealed that CXCL14 could specifically bind to trophoblast cells but not decidual cells from the maternal-fetal interface. These results suggest that CXCL14 plays an important role in regulating trophoblast invasion through an autocrine/paracrine manner during early pregnancy.

Interleukin-27 Inhibits Trophoblast Cell Invasion and Migration by Affecting the Epithelial–Mesenchymal Transition in Preeclampsia

2018 ◽  
Vol 26 (7) ◽  
pp. 928-938 ◽  
Author(s):  
Huisheng Ge ◽  
Nanlin Yin ◽  
Ting-Li Han ◽  
Dongni Huang ◽  
Xuehai Chen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Signal Transducer ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Epithelial Phenotype ◽  
And Migration

Preeclampsia (PE) is a pregnancy-specific disorder representing a major cause of maternal and perinatal morbidity and mortality. Invasive and migratory phenotypes are acquired by trophoblasts through the process of epithelial–mesenchymal transition (EMT). Studies have shown that trophoblast EMT events are dysregulated in PE and play an important role in its development. Dysregulation of interleukin (IL)-27 and IL-27R (T-cell cytokine receptor (TCCR)/WSX -1) is relevant to PE. In this study, our results demonstrated that IL-27 did not significantly affect the proliferation and apoptosis of HTR -8/SVneo trophoblast cells, while it did significantly inhibit trophoblast invasion and migration. The expression of EMT-related proteins in HTR-8/SVneo cells and extravillous explants was detected after treatment with IL-27. Expression of epithelial markers was increased, and mesenchymal marker expression was reduced. Furthermore, we found that IL-27 could induce significant phosphorylation of Signal Transducer and Activator of Transcription 1 (STAT1) and Signal Transducer and Activator of Transcription 3 (STAT3) in a time-dependent manner in HTR-8/SVneo cells. Selective inhibitors of STAT1 (STAT1 siRNA) and STAT3 (STAT3 siRNA) were used to determine whether both STAT1 and STAT3 are required for IL-27-mediated inhibition of EMT. STAT1 inhibition in IL-27-treated cells attenuated the IL-27 effect, while the inhibition of STAT3 activation had no effect on the development of the epithelial phenotype. These results demonstrate that IL-27 may inhibit trophoblast cell migration and invasion by affecting the EMT process through an STAT1-dominant pathway in PE.

scholarly journals The Increased lncRNA MIR503HG in Preeclampsia Modulated Trophoblast Cell Proliferation, Invasion, and Migration via Regulating Matrix Metalloproteinases and NF-κB Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Dan Cheng ◽  
Shan Jiang ◽  
Jiao Chen ◽  
Jie Li ◽  
Liangfei Ao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Western Blot ◽  
Trophoblast Cell ◽  
Migration Flow ◽  
Expression Levels ◽  
Invasion And Migration ◽  
And Migration

Background. Preeclampsia (PE) is a pregnancy-related syndrome characterized by hypertension and proteinuria after the 20th week of gestation. The long noncoding RNAs (lncRNAs) have been recently discovered for their roles in the pathogenesis of PE. This study is aimed at determining the expression of lncRNA MIR503 host gene (MIR503HG) in PE placental tissues and exploring the molecular mechanism underlying MIR503HG-mediated trophoblast cell proliferation, invasion, and migration. Methods. The expression level of MIR503HG in placental tissues, HTR-8/SVneo, and JEG3 cells was determined by quantitative real-time PCR; western blot detected the relevant protein expression levels in HTR-8/SVneo and JEG3 cells; flow cytometry determined cell apoptosis and cell cycle of HTR-8/SVneo and JEG3 cells; trophoblast cell proliferation, invasion, and migration of HTR-8/SVneo and JEG3 cells were measured by CCK-8, transwell invasion, and wound healing assays, respectively. Results. The highly expressed MIR503HG was detected in PE placental tissues compared to normal placental tissues. MIR503HG overexpression suppressed cell proliferation, invasion, and migration of HTR-8/SVneo and JEG3 cells, while knockdown of MIR503HG increased trophoblast cell proliferation, invasion, and migration. Flow cytometry results showed that MIR503HG overexpression induced apoptosis and caused cell cycle arrest at the G0/G1 phase, while MIR503HG knockdown had the opposite actions in HTR-8/SVneo and JEG3 cells. Western blot assay results showed that MIR503HG overexpression suppressed the matrix metalloproteinase-2/-9 and the snail protein expression and increased the E-cadherin expression in trophoblast cells. In addition, MIR503HG overexpression suppressed the NF-κB signaling pathway by inhibiting the phosphorylation of IκBα and the nuclear translocation of NF-κB signaling subunit p65. On the other hand, MIR503HG knockdown played an opposite role in these protein expression levels. Conclusion. Our results showed that MIR503HG inhibited the proliferation, invasion, and migration of HTR-8/SVneo and JEG3 cells, which may be related to the pathogenesis of PE.

scholarly journals The effect of IL-6 on the trophoblast cell line HTR-8/SVneo

2010 ◽  
Vol 62 (3) ◽  
pp. 531-538 ◽  
Author(s):  
Milica Jovanovic ◽  
Tamara Kovacevic ◽  
Ivana Stefanoska ◽  
Ljiljana Vicovac
Keyword(s):  
Cell Line ◽  
Normal Pregnancy ◽  
Blastocyst Stage ◽  
Uterine Wall ◽  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Invasion And Migration ◽  
And Migration ◽  
Trophoblast Cell Line

Embryonic development up to the blastocyst stage, implantation into the uterine wall and the development of the functional placenta are steps crucial for the establishment of normal pregnancy. Specific cells of the placenta, the trophoblast cells, invade the uterine stroma and spiral arteries, adapting them to pregnancy. Interleukin-6 is present in the human endometrium during the receptive phase and early pregnancy. Trophoblasts also produce IL-6, which was found to stimulate trophoblast invasion and migration in vitro. Here we show that the activity of MMP-9 may contribute to the observed increased invasion. In addition, in the HTR-8/SVneo trophoblast cell line IL-6 increases cell proliferation. .

scholarly journals Role of placenta-specific protein 1 in trophoblast invasion and migration

Reproduction ◽  
2014 ◽  
Vol 148 (4) ◽  
pp. 343-352 ◽  
Author(s):  
Wen-Lin Chang ◽  
Qing Yang ◽  
Hui Zhang ◽  
Hai-Yan Lin ◽  
Zhi Zhou ◽  
...  
Keyword(s):  
First Trimester ◽  
Specific Protein ◽  
Trophoblast Invasion ◽  
Specific Gene ◽  
Invasion And Migration ◽  
Functional Studies ◽  
And Migration ◽  
Extravillous Trophoblasts

Placenta-specific protein 1 (PLAC1), a placenta-specific gene, is known to be involved in the development of placenta in both humans and mice. However, the precise role of PLAC1 in placental trophoblast function remains unclear. In this study, the localization of PLAC1 in human placental tissues and its physiological significance in trophoblast invasion and migration are investigated by technical studies including real-time RT-PCR, in situ hybridization, immunohistochemistry, and functional studies by utilizing cell invasion and migration assays in the trophoblast cell line HTR8/SVneo as well as the primary inducing extravillous trophoblasts (EVTs). The results show that PLAC1 is mainly detected in the trophoblast columns and syncytiotrophoblast of the first-trimester human placental villi, as well as in the EVTs that invade into the maternal decidua. Knockdown of PLAC1 by RNA interference significantly suppresses the invasion and migration of HTR8/SVneo cells and shortens the distance of the outgrowth of the induced EVTs from the cytotrophoblast column of the explants. All the above data suggests that PLAC1 plays an important role in human placental trophoblast invasion and migration.

scholarly journals EphA2-mediatedM1-like polarization of microglia attenuatesglioblastoma metastasis

2020 ◽  
Author(s):  
Xiang Liao ◽  
Ru Fang ◽  
Ying Tian ◽  
Chen Chen ◽  
Zhijun Wu ◽  
...  
Keyword(s):  
Western Blot ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Attractive Therapeutic Target ◽  
And Migration ◽  
Tissue Specimens

Abstract BackgroundEphA2 is upregulated in GBM tumor tissue specimens and established cancer cell lines and thought to be an attractive therapeutic target in cancer. We aim to define the role of EphA2 in polarization of microglia.MethodsQuantitative real-time polymerase chain reaction, immunofluorescence staining, and viral transfection-based knockdown and overexpression assays to assess the effect of EphA2 on microglia polarization. iTRAQ-LC-MS/MS and western blot were conducted to detect EphA2 and PI3K-Akt signaling activity. Using the Millicell system as an in vitro co-culture model, we performed transwell and western blot assays investigate the role of EphA2-mediated M1-like of microglia on GBM cells invasion and migration in vitro and in vivo. ResultsIn overexpressing and silencing experiments, we demonstrated that EphA2 contributed to the M1-like polarization of microglia. Mechanistically, PI3K-AKT signaling was the downstream of EphA2 and supported the process of EphA2 mediated the M1-like polarization of microglia. Finally, EphA2 mediated the M1-like polarization of microglia attenuated the migration and invasion ability of GBM cells in vitro and in vivo.ConclusionsOur study indicates that, distinct from its role on cancer cells, EphA2 promoted the M1-like polarization of microglia and further attenuated the metastasis of GBM.Our results provide a new information on rationale for targeting EphA2 to improve treatment outcomes in GBM patients.

Expression of N-Acetylglucosaminyltransferase III Promotes Trophoblast Invasion and Migration in Early Human Placenta

2018 ◽  
Vol 26 (10) ◽  
pp. 1373-1381
Author(s):  
Qinyin Deng ◽  
Xiru Liu ◽  
Zhongmei Yang ◽  
Lan Xie
Keyword(s):  
Flow Cytometric Analysis ◽  
Gelatin Zymography ◽  
Placental Tissue ◽  
First Trimester ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Trophoblast Invasion ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Decidual Cells ◽  
And Migration

Introduction: Trophoblast migration and invasion at the maternal–fetal interface are crucial events for normal placentation and successful pregnancy. This progress is well controlled by many placenta-specific factors. Inadequate trophoblast invasion results in poor placenta plantation or even complications such as preeclampsia. It has been shown that N-acetylglucosaminyltransferase III (GnT-III) participates in tumor invasion and metastasis as a suppressor; however, the expression of GnT-III and its role in normal pregnancy is unclear. Our objective was to characterize GnT-III expression and function during placental development and identify the underlying mechanisms. Methods: The expression of GnT-III in human placental tissue from the first trimester was determined by immunohistochemistry. The HTR8/SVneo cell line was used to investigate the effects of GnT-III on proliferation, apoptosis, migration/invasion, matrix metalloproteinase (MMP) 2/9 activity, and the expression of the tissue inhibitor of metalloproteinase (TIMP) 1/2 using cell 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, flow cytometric analysis, transwell migration/invasion assays, gelatin zymography, and Western blot, respectively. Moreover, a placental villous explant model was employed to determine its functions in placentation. Results: In the first-trimester placental tissue, GnT-III was localized within the cytotrophoblast, the syncytiotrophoblast and the trophoblast columns of human placental villi, decidual cells, and some extravillous cells in the maternal decidua. GnT-III silencing significantly inhibited HTR8/SVneo cell invasion and migration as well as extravillous explant outgrowth. The application of GnT-III siRNA significantly attenuated MMP2/9 activity and increased TIMP1/2 expression. Discussion and Conclusion: GnT-III is expressed in trophoblasts during normal human pregnancy and is involved in regulating trophoblast function.

Sign in / Sign up

Export Citation Format

Share Document