Invasion Of Choriocarcinoma Cells Research Articles

Rolipram suppresses migration and invasion of human choriocarcinoma cells by inhibiting phosphodiesterase 4-mediated epithelial-mesenchymal transition.

Rolipram is a selective phosphodiesterase-4 (PDE4) inhibitor. The effect of rolipram on the metastasis of choriocarcinoma is barely known. Here, we evaluated the role of rolipram in the migration and invasion of human choriocarcinoma cells in vitro.Human choriocarcinoma cells lines JEG3 and JAR were used in this study. The expression profile of PDE4 subfamily members in choriocarcinoma cells was evaluated using real-time PCR. The migration and invasion properties of choriocarcinoma cells before and after inhibition of PDE4 by rolipram or RNAi-directed knockdown were evaluated in vitro. Expression levels of MMP9, TIMP1, E-cadherin, vimentin, TGFβ1, SMAD1, and SMAD4 of choriocarcinoma cells were compared before and after rolipram treatment, RNAi-directed knockdown of PDE4D, and overexpression of PDE4D. We found PDE4D was the most commonly expressed isoform of PDE4 both in JEG3 and JAR cells. Rolipram and knockdown of PDE4D were efficient to inhibit the migration and invasion of choriocarcinoma cells in vitro, accompanied by decreased expression of MMP9 and TIMP1. Furthermore, rolipram and knockdown of PDE4D promoted the expression of E-cadherin but reduced the expression of vimentin in choriocarcinoma cells, and overexpression of PDE4D decreased the expression of E-cadherin but promoted the expression of vimentin. Rolipram suppressed migration and invasion of human choriocarcinoma cells in vitro, possibly by inhibiting epithelial-mesenchymal transition through PDE4 inhibition.

Extracellular vesicle-mediated delivery of miR-127-3p inhibits the proliferation and invasion of choriocarcinoma cells by targeting ITGA6

BackgroundChoriocarcinoma (CC) is a highly aggressive malignant tumor that mostly occurs in women of childbearing age. Chemotherapy is the main treatment for CC, but it has side effects and causes drug resistance, which can lead to treatment failure. Extracellular vesicles (EVs) that deliver microRNAs (miRNAs) have emerged as a novel and promising therapeutic tool for inhibiting tumor progression and metastasis. This research aimed to study the effects of miR-127-3p-enriched EVs (EV-miR-127-3p) on CC and underlying mechanisms. MethodsQuantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to determine the miR-127-3p and integrin subunit alpha-6 (ITGA6) expression levels. The interaction between miR-127-3p and ITGA6 was confirmed by a dual-luciferase reporter assay. Human umbilical cord mesenchymal stem cells (hUCMSCs) were identified using flow cytometry and multilineage differentiation. Uptake of labeled EVs was demonstrated using immunofluorescence staining and flow cytometry assays. EV-miR-127-3p were isolated from the culture medium of hUCMSCs and co-cultured with JEG-3 or JAR cells to evaluate their effects on cell proliferation, invasion, migration, and apoptosis, using the cell counting kit-8, Transwell, and flow cytometry assays. Epithelial-mesenchymal transition (EMT) and the transforming growth factor (TGF)-β1/Smad pathway were investigated using qRT-PCR and western blotting. ResultsThe expression of miR-127-3p was downregulated, while that of ITGA6 was upregulated in CC cell lines. ITGA6 was identified as a target gene of miR-127-3p. EV-miR-127-3p could inhibit the proliferation, invasion, migration, and promote the apoptosis of CC cells. We observed that EV-miR-127-3p suppressed EMT of CC cells by targeting ITGA6. In addition, the knockdown of ITGA6 inhibited the TGF-β1/Smad pathway and reversed the EMT-promoting effect. ConclusionThese results indicate that EV-miR-127-3p from hUCMSCs exhibits anti-tumor effects by targeting ITGA6, which may be used as a novel therapeutic strategy for CC treatment.

Ropivacaine Retards the Viability, Migration, and Invasion of Choriocarcinoma Cells by Regulating the Long Noncoding RNA OGFRP1/MicroRNA-4731-5p/HIF3A Axis.

Choriocarcinoma is an aggressive gestational trophoblastic neoplasm. This study attempted to explore the biological functions and underlying mechanisms by which ropivacaine restrains the progression of choriocarcinoma. The expression of long noncoding RNA OGFRP1, microRNA-4731-5p (miR-4731-5p), and HIF3A in choriocarcinoma cells was assessed by qRT-PCR. Choriocarcinoma cells treated with ropivacaine at the concentration of 100, 500, and 1000μM were cultured for 24, 48, and 72h, respectively. Choriocarcinoma cell viability was evaluated by MTT assay. Transwell assay was conducted to examine choriocarcinoma cell migration and invasion. Additionally, the target relationship between OGFRP1 and miR-4731-5p or between miR-4731-5p and HIF3A was predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assays. OGFRP1 and HIF3A expression were enhanced in choriocarcinoma cells, while miR-4731-5p expression was inhibited. Treatment with ropivacaine impeded choriocarcinoma cell viability, migration, and invasion. Choriocarcinoma cells treated with 1000μM ropivacaine for 48h were selected for subsequent experiments. OGFRP1 elevation or miR-4731-5p deficiency mitigated the reduction effect of ropivacaine on tumorigenesis of choriocarcinoma cells. Besides, miR-4731-5p was predicted as the potential OGFRP1 target by StarBase and LncBase, and HIF3A was predicted as the potential miR-4731-5p target by StarBase and TargetScan. Dual-luciferase reporter assays determined that miR-4731-5p was a target of OGFRP1 and HIF3A was a target of miR-4731-5p. Feedback experiments declared that miR-4731-5p elevation or HIF3A suppression reversed the promoting effect of OGFRP1 overexpression on the malignant behaviors of ropivacaine-treated choriocarcinoma cells. Ropivacaine constrained choriocarcinoma cell viability, migration, and invasion through modulating the OGFRP1/miR-4731-5p/HIF3A axis. Our study may provide a novel strategy for choriocarcinoma prevention and treatment.

The (pro)renin receptor and soluble (pro)renin receptor in choriocarcinoma.

This study aimed to determine if the (pro)renin receptor (ATP6AP2) changes the cellular profile of choriocarcinomas from cytotrophoblast cells to terminally syncytialised cells and ascertain whether this impacts the invasive potential of choriocarcinoma cells. Additionally, we aimed to confirm that FURIN and/or site 1 protease (MBTPS1) cleave soluble ATP6AP2 (sATP6AP2) in BeWo choriocarcinoma cells and determine whether sATP6AP2 levels reflect the cellular profile of choriocarcinomas. BeWo choriocarcinoma cells were treated with ATP6AP2 siRNA, FURIN siRNA, DEC-RVKR-CMK (to inhibit FURIN activity), or PF 429242 (to inhibit MBTPS1 activity). Cells were also treated with forskolin, to induce syncytialisation, or vehicle and incubated for 48 h before collection of cells and supernatants. Syncytialisation was assessed by measuring hCG secretion (by ELISA) and E-cadherin protein levels (by immunoblot and immunocytochemistry). Cellular invasion was measured using the xCELLigence real-time cell analysis system and secreted sATP6AP2 levels measured by ELISA. Forskolin successfully induced syncytialisation and significantly increased both BeWo choriocarcinoma cell invasion (P < 0.0001) and sATP6AP2 levels (P = 0.02). Treatment with ATP6AP2 siRNA significantly inhibited syncytialisation (decreased hCG secretion (P = 0.005), the percent of nuclei in syncytia (P = 0.05)), forskolin-induced invasion (P = 0.046), and sATP6AP2 levels (P < 0.0001). FURIN siRNA and DEC-RVKR-CMK significantly decreased sATP6AP2 levels (both P < 0.0001). In conclusion, ATP6AP2 is important for syncytialisation of choriocarcinoma cells and thereby limits choriocarcinoma cell invasion. We postulate that sATP6AP2 could be used as a biomarker measuring the invasive potential of choriocarcinomas. Additionally, we confirmed that FURIN, not MBTPS1, cleaves sATP6AP2 in BeWo cells, but other proteases (inhibited by DEC-RVKR-CMK) may also be involved.

Core2 beta 1, 6-N acetylglcosaminyl transferase promotes invasion of choriocarcinoma cells through glycosylation to MICA and MUC1

Core2 beta 1, 6-N acetylglcosaminyl transferase promotes invasion of choriocarcinoma cells through glycosylation to MICA and MUC1

Identification of microRNA signature in the progression of gestational trophoblastic disease

Gestational trophoblastic disease (GTD) encompasses a range of trophoblast-derived disorders. The most common type of GTD is hydatidiform mole (HM). Some of HMs can further develop into malignant gestational trophoblastic neoplasia (GTN). Aberrant expression of microRNA (miRNA) is widely reported to be involved in the initiation and progression of cancers. MiRNA expression profile also has been proved to be the useful signature for diagnosis, staging, prognosis, and response to chemotherapy. Till now, the profile of miRNA in the progression of GTD has not been determined. In this study, a total of 34 GTN and 60 complete HMs (CHM) trophoblastic tissues were collected. By miRNA array screening and qRT-PCR validating, six miRNAs, including miR-370-3p, -371a-5p, -518a-3p, -519d-3p, -520a-3p, and -934, were identified to be differentially expressed in GTN vs. CHM. Functional analyses further proved that miR-371a-5p and miR-518a-3p promoted proliferation, migration, and invasion of choriocarcinoma cells. Moreover, we demonstrated that miR-371a-5p was negatively related to protein levels of its predictive target genes BCCIP, SOX2, and BNIP3L, while miR-518a-3p was negatively related to MST1 and EFNA4. For the first time, we proved that miR-371a-5p and miR-518a-3p directly targeted to 3′-UTR regions of BCCIP and MST1, respectively. Additionally, we found that miR-371a-5p and miR-518a-3p regulated diverse pathways related to tumorigenesis and metastasis in choriocarcinoma cells. The results presented here may offer new clues to the progression of GTD and may provide diagnostic biomarkers for GTN.

C-Rel Promotes Invasion of Choriocarcinoma Cells via PI3K/AKT Signaling

Objective: Choriocarcinoma is the most common epithelial cancer among gestational trophoblastic diseases (GTDs); the mechanism of trophoblastic carcinogenesis is unknown. This study aimed to examine the expression of NF-κB family proteins in GTDs and placental tissues as well as the roles of c-Rel in choriocarcinoma. Methods: We examined the expression of NF-κB family proteins in normal placenta and hydatidiform mole tissues as well as extravillous trophoblast (EVT) and choriocarcinoma cell lines by Western blot and immunohistochemistry. Immunoprecipitation was performed to determine which proteins can bind with c-Rel in choriocarcinoma cells. To investigate the roles of c-Rel in choriocarcinoma, we examined the effects of c-Rel knockdown and overexpression on cell proliferation, migration, and invasion using small interfering RNAs and gene activation plasmid. Results: The expression of c-Rel was strong in choriocarcinoma and EVTs, but very weak in villi of normal placenta and hydatidiform mole. Immunoprecipitation suggested that c-Rel heterodimerizes with p65 in choriocarcinoma. c-Rel knockdown reduced invasion, migration, and AKT phosphorylation in choriocarcinoma cells. c-Rel overexpression in choriocarcinoma increased migratory and invasive abilities, and the effect on invasion was inhibited by a PI3K inhibitor. Conclusion: These findings suggest that c-Rel might play a role in promoting the invasion of choriocarcinoma cells through PI3K/AKT signaling.

Nodal signals via β-arrestins and RalGTPases to regulate trophoblast invasion

Placentation is critical for establishing a healthy pregnancy. Trophoblasts mediate implantation and placentation and certain subtypes, most notably extravillous cytotrophoblast, are highly invasive. Trophoblast invasion is tightly regulated by microenvironmental cues that dictate placental morphology and depth. In choriocarcinomas, malignant trophoblast cells become hyperinvasive, breaching the myometrium and leading to major complications. Nodal, a member of the TGF-β superfamily, is expressed throughout the endometrium during the peri-implantation period and in invasive trophoblast cells. Nodal promotes the invasion of numerous types of cancer cells. However, Nodal's role in trophoblast and choriocarcinoma cell invasion is unclear. Here we show that Nodal stimulates the invasion of both the non-malignant HTR-8SV/neo trophoblast and JAR choriocarcinoma cells in a dose-dependent manner. We found that endogenous β-arrestins and Ral GTPases, key regulators of the cell cytoskeleton, are constitutively associated with Nodal receptors (ALK4 and ALK7) in trophoblast cells and that RalA is colocalized with ALK4 in endocytic vesicles. Nodal stimulates endogenous β-arrestin2 to associate with phospho-ERK1/2, and knockdown of β-arrestin or Ral proteins impairs Nodal-induced trophoblast and choriocarcinoma cell invasion. These results demonstrate, for the first time, that β-arrestins and RalGTPases are important regulators of Nodal-induced invasion.

Suppression of choriocarcinoma invasion and metastasis following blockade of BDNF/TrkB signaling

Brain-derived neurotrophic factor (BDNF) acts through its cognate receptor tyrosine kinase-B (TrkB) to regulate diverse physiological functions in reproductive and other tissues. In normal and malignant trophoblastic cells, the BDNF/TrkB signaling promotes cell growth. Due to the highly malignant nature of choriocarcinoma, we investigated possible involvement of this system in choriocarcinoma cell invasion and metastasis. We demonstrated that treatment of cultured choriocarcinoma cells, known to express both BDNF and TrkB, with a soluble TrkB ectodomain or a Trk receptor inhibitor K252a suppressed cell invasion accompanied with decreased expression of matrix metalloproteinase-2, a cell invasion marker. In vivo studies using a tumor xenograft model in athymic nude mice further showed inhibition of cell invasion from tumors to surrounding tissues following the suppression of endogenous TrkB signaling. For an in vivo model of choriocarcinoma metastasis, we performed intravenous injections of JAR cells expressing firefly luciferase into severe combined immunodeficiency (SCID) mice. Treatment with K252a inhibited metastasis of tumors to distant organs. In vivo K252a treatment also suppressed metastatic tumor growth as reflected by decreased cell proliferation and increased apoptosis and caspases-3/7 activities, together with reduced tissue levels of a tumor marker, human chorionic gonadotropin-β. In vivo suppression of TrkB signaling also led to decreased expression of angiogenic markers in metastatic tumor, including cluster of differentiation 31 and vascular endothelial growth factor A. Our findings suggested essential autocrine/paracrine roles of the BDNF/TrkB signaling system in choriocarcinoma invasion and metastasis. Inhibition of this signaling could serve as the basis to develop a novel therapy for patients with choriocarcinoma.

Abstract 4938: Free β-subunit of human chorionic gonadotropin stimulates choriocarcinoma cell invasion independent of LH/hCG receptor.

Abstract Human chorionic gonadotropin (hCG) is a heterodimer consisting of an α- and a β-subunit (hCGα and hCGβ) that are non-covalently linked. Intact hCG, but not free subunits, bind to the LH/hCG receptor. Expression of hCG and hCGβ has been observed in several cancers. Most trophoblastic tumors of placental and germ cell origin produce hCG, while many non-trophoblastic tumors, including bladder, renal and gastrointestinal cancers, often produce hCGβ, and increased serum concentrations of these are associated with adverse prognosis. hCG has been found to stimulate trophoblast invasion. The stimulatory activity has especially been ascribed to a hyperglycosylated form of hCG (hCG-h) expressed in early pregnancy. hCG-h is also a major form of hCG produced by choriocarcinoma and by testicular cancers, although tumor-derived hCG-h is often glycosylated differently than that produced by the placenta. We aimed to compare different forms of hCG in their stimulatory activities on the invasion of JEG-3 choriocarcinoma cells. Various forms of hCG and hCGβ were purified from urine of one patient with nonseminomatous testicular cancer, one with invasive molar disease, and pregnant women. Both hCG and hCGβ, and their hyperglycosylated forms stimulated the invasion of JEG-3 cells. However, cancer-derived hCG-h was more effective than “regular” hCG in stimulating the invasion. Down-regulation of the LH/hCG receptor by RNA-interference did not significantly reduce the effect of hCGβ and hCG on cell invasion. Increased invasion was associated with increased activity of MMP-2, MMP-9 and uPA in conditioned culture medium from JEG-3 cells. Our findings suggest that hCG and hCGβ stimulates the invasion of choriocarcinoma cells independent of the classical LH/hCG-receptor. Citation Format: Cheuk-Lun Lee, Philip CN Chiu, Laura Hautala, William SB Yeung, Ulf-Håkan Stenman, Hannu Koistinen. Free β-subunit of human chorionic gonadotropin stimulates choriocarcinoma cell invasion independent of LH/hCG receptor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4938. doi:10.1158/1538-7445.AM2013-4938

Intranuclear Crosstalk between Extracellular Regulated Kinase1/2 and Signal Transducer and Activator of Transcription 3 Regulates JEG‐3 Choriocarcinoma Cell Invasion and Proliferation

Invasiveness of trophoblast and choriocarcinoma cells is in part mediated via leukemia inhibitory factor- (LIF-) induced activation of signal transducer and activator of transcription 3 (STAT3). The regulation of STAT3 phosphorylation at its ser727 binding site, possible crosstalk with intracellular MAPK signaling, and their functional implications are the object of the present investigation. JEG-3 choriocarcinoma cells were cultured in presence/absence of LIF and the specific ERK1/2 inhibitor (U0126). Phosphorylation of signaling molecules (p-STAT3 (ser727 and tyr705) and p-ERK1/2 (thr 202/tyr 204)) was assessed per Western blot. Immunocytochemistry confirmed results, but also pinpointed the location of phosphorylated signaling molecules. STAT3 DNA-binding capacity was studied with a colorimetric ELISA-based assay. Cell viability and invasion capability were assessed by MTS and Matrigel assays. Our results demonstrate that LIF-induced phosphorylation of STAT3 (tyr705 and ser727) is significantly increased after blocking ERK1/2. STAT3 DNA-binding capacity and cell invasiveness are enhanced after LIF stimulation and ERK1/2 blockage. In contrast, proliferation is enhanced by LIF but reduced after ERK1/2 inhibition. The findings herein show that blocking ERK1/2 increases LIF-induced STAT3 phosphorylation and STAT3 DNA-binding capacity by an intranuclear crosstalk, which leads to enhanced invasiveness and reduced proliferation.

Fractal dimension of the choriocarcinoma cell invasion front

The Minkowski dimension was calculated for the determination of the invasiveness of cancer cells, which were brought in close contact (confronted) to host tissues and cultivated in vitro. The confrontation cultures were histologically sectioned and stained immunohistochemically. Digital images of these sections were segmented, processed and the specimens’ boundaries were investigated. The invasion front was treated as a fractal. The value of the Minkowski dimension increased with increased invasiveness of the cells. The Minkowski dimension could be used as a quantitative measure for cancer diagnosis.

IGF-II regulates metastatic properties of choriocarcinoma cells through the activation of the insulin receptor

Choriocarcinoma is a highly malignant tumor that can arise from trophoblasts of any type of gestational event but most often from complete hydatidiform mole. IGF-II plays a fundamental role in placental development and may play a role in gestational trophoblastic diseases. Several studies have shown that IGF-II is expressed at high levels in hydatidiform moles and choriocarcinoma tissues; however, conflicting data exist on how IGF-II regulates the behaviour of choriocarcinoma cells. The purpose of this study was to determine the contribution of the receptors for IGF-I and insulin to the actions of IGF-II on the regulation of choriocarcinoma cells metastasis. An Immuno Radio Metric Assay was used to analyse the circulating and tissue levels of IGF-I and IGF-II in 24 cases of hydatidiform mole, two cases of choriocarcinoma and eight cases of spontaneous abortion at the same gestational age. The JEG-3 choriocarcinoma cell line was used to investigate the role of IGF-II in the regulation of cell invasion. We found that mole and choriocarcinoma tissue express high levels of IGF-II compared to first trimester placenta. Both IGF-I and IGF-II regulate choriocarcinoma cell invasion in a dose dependent manner but through a different mechanism. IGF-II effects involve the activation of the InsR while IGF-I uses the IGF-IR. The positive effects of IGF-II on invasion are the result of enhanced cell adhesion and chemotaxis (specifically towards collagen IV). The actions of IGF-II but not those of IGF-I were sensitive to inhibition by the insulin receptor inhibitor HNMPA(AM)3. Our results demonstrate that the insulin receptor regulates choriocarcinoma cell invasion.

The use of Alamar Blue assay for quantitative analysis of viability, migration and invasion of choriocarcinoma cells

The current techniques for quantifying trophoblast viability, migration and invasion are mainly limited by the need to sacrifice the cells during the test procedure. In this study, the vital dye AB (AB) was used to quantify cell number and viability of BeWo and JEG-3 choriocarcinoma cells, as well as their migration and invasion through fibronectin-coated filters. AB was directly added to culture medium of incubated test and control cells. At various time intervals, the redox reaction, in which AB is reduced by the cells, was measured by absorbance readings at 540 and 630 nm. For cell migration and invasion, cells were cultured onto uncoated or fibronectin-coated inserts, respectively. AB reduction of migrated cells was normalized to that of control cells to calculate percentages of migration. This model was also tested in the presence of a reported inhibitor, transforming growth factor (TGF) beta. The curve of %AB reduction versus cell number was linear, with intra- and inter-assay Coefficient of Variations of 1.88%and 2.94%, respectively. AB reduction increased with both seeding concentrations and incubation time with AB. TGFbeta treatment caused a modest decrease in AB reduction in both JEG-3 and BeWo cells. TGFbeta treatment also decreased migration in BeWo, but not in JEG-3, cells. AB assay is a simple and reliable method for quantifying trophoblast viability, migration and invasion.

Gestational trophoblastic diseases: 1. Pathophysiology of hyperglycosylated hCG

Objective. Hyperglycosylated hCG (hCG-H) is a glycosylation variant of hCG produced by cytotrophoblast cells at implantation of pregnancy and in choriocarcinoma. We investigated the biological function of hCG-H in invasion in vitro and in vivo and the use of hCG-H antibodies in blocking tumorigenesis and cancer growth in vivo. Methods and results. hCG-H accounts for 43% to 100% of total hCG immunoreactivity in the culture fluid of choriocarcinoma cell lines and 100% in primary cultures of pregnancy cytotrophoblast cells. We investigated the action of hCG and hCG-H on isolated cytotrophoblast cell primary cultures and on 3 different lines of choriocarcinoma cells cultured on Matrigel basement membrane inserts (culture models for assessing tumor invasion). The addition of hCG-H to medium significantly promoted invasion of membranes with both pregnancy and cancer cell line sources, while regular hCG had no significant effect. JEG-3 human choriocarcinoma cells were transplanted subcutaneously into athymic nude mice. Tumors rapidly formed. B152, mouse monoclonal antibody against hCG-H, and non-specific mouse IgG (control) were administered twice weekly once tumors were clearly visible. While a correlation between time and growth was observed with the control group ( r 2 = 0.97), no correlation was observed with the B152-treated mice ( r 2 = 0.15). B152 blocked tumor growth ( t test, IgG vs. B152, P = 0.003). In a second experiment, antibody B152 or IgG was administered to mice at the time of choriocarcinoma transplantation. B152 significantly inhibited tumorigenesis ( t test P = 0.0071). Conclusions. hCG-H is a critical promoter in human cytotrophoblast and human choriocarcinoma cell invasion in vivo and in vitro, promoting tumor growth and invasion through an autocrine mechanism. hCG-H is a signal for choriocarcinoma cell invasion, making it a biological tumor marker. Antibodies against hCG-H block tumor formation and growth. Human or humanized antibodies against hCG-H may be useful in treating and managing choriocarcinoma and other gestational trophoblastic malignancies.

Angiotensin II Augmented Migration and Invasion of Choriocarcinoma Cells Involves PI3K Activation Through the AT1 Receptor

While angiotensin II (Ang II) has been shown to inhibit migration of extravillous trophoblasts via plasminogen activator inhibitor-1 (PAI-1) activation, it has remained unclear whether it stimulates or inhibits malignant behavior of choriocarcinoma cells. Since we previously found an involvement of the renin-angiotensin system (RAS) in the proliferative potential in choriocarcinoma cells (BeWo), mediated via the Ang II type 1 receptor (AT1R), in the present study we investigated the effects of Ang II on choriocarcinoma cell migration/invasion in vitro using Transwell cell culture chambers. Ang II (10(-8)M) promoted migration and invasion by a choriocarcinoma cell line and augmented random cell mobility on checkerboard analysis. Immunoblotting showed Ang II to activate the phosphorylation of FAK and Akt in BeWo cells. Furthermore Ang II effects on cell migration were abolished by a selective AT1R antagonist and a phosphatidylinositol 3-kinase (PI3K) inhibitor. The present results suggest that Ang II-induced migration and invasion of choriocarcinoma cells probably involves PI3K following binding to the AT1R.

Human chorionic gonadotrophin reduces matrix metalloproteinases expression in JEG-3 choriocarcinoma cell line

Objective To uncover the effect of human chorionic gonadotrophin (hCG) on the invasion of choriocarcinoma cells.Methods The effect of hCG on the expression of matrix metalloproteinases (MMPs) in JEG\|3 choriocarcinoma cell line was investigated by applying the method of reverse transcription polymerase chain reaction (RT\|PCR). Results The results showed that, among the 18 types of MMPs only MMP\|8,\|10, \|12,\|19 were found to be expressed by JEG\|3 cells. After the incubation with 25 IU/ml hCG for 50hours, the expression of these 4 types of MMPs were all significantly reduced. Conclusion The invasiveness of JEG\|3 choriocarcinoma cell line was associated with the expression of MMP\|8, \|10, \|12, \|19, high levels of hCG could reduce the invasion of choriocarcinoma cells by inhibiting MMPs expression.

Investigations on the invasion of choriocarcinoma cells grown as spheroids

Investigations on the invasion of choriocarcinoma cells grown as spheroids