Placenta-specific Protein Research Articles

Placenta-specific protein 1 enhances liver metastatic potential and is associated with the PI3K/AKT/NF-κB signaling pathway in colorectal cancer.

To better explore the underlying mechanism of liver metastatic formation by placenta-specific protein 1 (PLAC1) in human colorectal cancer, we investigated the proliferation, invasion and angiogenic capabilities of human colorectal cancer cells with different liver metastatic potentials as well as the mechanism of action of PLAC1 in the metastatic process. The expression of PLAC1 was detected by reverse transcriptase PCR, western blot, and real-time PCR. The effect of PLAC1 on metastatic potential was determined by proliferation, invasion, and angiogenesis assays, including an in-vitro coculture system consisting of cancer cells and vascular endothelial cells that were used to detect the relationship between cancer cells and angiogenesis. In addition, we also determined PLAC1 downstream targets that preferentially contribute to the metastatic process. PLAC1 was expressed in HT-29, WiDr, and CaCo-2 colorectal cancer cells but not in Colo320 colorectal cancer cells. PLAC1 not only enhanced significantly the proliferation of CoLo320 and human umbilical vein endothelial cells (HUVECs) but also promoted the invasion of CoLo320 cells. The angiogenesis of HUVECs was enhanced by PLAC1 in a dose-dependent manner. In cocultured systems, angiogenesis was significantly increased by coculture with HT-29 cells. In addition, PLAC1 could promote angiogenesis in coculture with HT-29 cells. Furthermore, PLAC1-enhanced metastatic potential of colorectal cancer cells was dependent on the activation of the PI3K/Akt/NF-κB pathway. The activation of PI3K/Akt/NF-κB signaling by PLAC1 may be critical for metastasis of colorectal cancer cells. According to our results, we suggest that modification of PLAC1 function might be a promising new therapeutic approach to inhibit the aggressive spread of colorectal cancer.

M6A RNA Methylation Regulators Contribute to Eutopic Endometrium and Myometrium Dysfunction in Adenomyosis.

Adenomyosis is a prevalent, estrogen-dependent uterine disorder wherein endometrial cells are abnormally present in the myometrium and are surrounded by hyperplastic/hypertrophic smooth muscle. Its etiology is unclear, although endometrial cell invasion into the myometrium has been postulated. RNA methylation, particularly N6-methyladenosine (m6A), plays an important role in regulating various physiological processes and invasive disorders. The goal of this in silico and lab-based experimental study was to explore a possible role for m6A in adenomyosis. Gene expression profiles of both the endometrium and myometrium of women with adenomyosis (cases) and without disease (controls) were obtained from the publicly available Gene Expression Omnibus (GEO) database. In the endometrium, STRING database analysis revealed that METTL3 functions as a “hub” gene of m6A RNA methylation regulators, and the genes involved in m6A regulation, including METTL3, FTO, ZC3H13, and YTHDC1 expression, were significantly decreased in cases versus controls. Functional, co-expression, and correlational analyses of endometrium from cases versus controls revealed decreased total m6A levels, induced by METTL3, and the downstream elevated insulin−like growth factor−1(IGF1) and D-Dopachrome Tautomerase (DDT), with the latter two having known functions in epithelial proliferation and cell migration, which are important processes in the pathogenesis of adenomyosis in endometrium. m6A RNA methylation regulators, including RBM15/15B, ALKBH5, FTO, YTHDF1/2, KIAA1429, HNRNPC, METTL3, ZC3H13, and YTHDC2, were also differentially expressed in the myometrium from cases versus controls. We validated decreased total m6A levels and differential expression of m6A RNA methylation regulators in the myometrium of patients with adenomyosis using qRT-PCR, immunohistochemistry and tissues available from our biorepository. Possible target genes, including cadherin 3(CDH3), sodium channelβ-subunit 4 (SCN4B), and placenta-specific protein 8 (PLAC8), which are involved in cell adhesion, muscle contraction and immune response in the myometrium of adenomyosis patients were also validated. Thus, through extensive public database mining and validation of select genes, this study, for the first time, implicates m6A and its methylation regulators in the pathogenesis of adenomyosis. Follow on functional studies are anticipated to elucidate mechanisms involving m6A and its regulators and down-stream effectors in the pathogenesis of this enigmatic reproductive disorder and potentially identify druggable targets to control its associated symptoms.

In silico Evaluation of PLAC1-fliC As a Chimeric Vaccine against Breast Cancer

Background:Breast cancer is one of the most prevalent cancers among women. Common cancer treatment methods are not effective enough, and there is a need for a more efficient treatment procedure. Cancer vaccine is a novel immunotherapy method that stimulates humoral and/or cellular immunity against cancer. PLAC1 is a cancer/testis antigen, prevalent in breast cancer and rarely found in normal tissues. FliC, as a bacterial adjuvant, when fused to PLAC1 can elicit humoral and cellular responses. Therefore, PLAC1-fliC is a chimeric protein, which can be considered a suitable candidate against breast cancer. Methods:ProtParam was used to evaluate the physicochemical properties of PLAC1-fliC. Second structures were determined using the GOR V server. PLAC1-fliC 3D structure was modeled by Phyre2, and it was refined using GalaxyWEB. The refined model was submitted to RAMPAGE, PROCHECK, and ProSA-web for validation. Antigenicity and allergenicity of the construct were predicted by ANTIGENpro, VaxiJen, AllergenFP, and SDAP databases. Then MHC-I- and MHC-II-binding epitopes of PLAC1-fliC were forecasted by NetMHC 4.0 and NetMHCII 2.3 Servers. Finally, Ellipro and CTLpred were employed to predict B-cell and CTL epitopes. Results:The construct was evaluated as a stable fusion protein, which could be antigenic and could stimulate B and T cells against breast cancer. Conclusion:PLAC1-fliC, as a cancer vaccine candidate, might be suitable and specific for breast cancer, which could evoke humoral and cellular immunity against this type of tumor.

905: Release of placental exosomes is reduced in spontaneous preterm births

Feto-maternal signaling is considered to contribute to the timing of birth. Exosomes originating from the placenta may transport signals to maternal tissues where they deposit protein and RNA cargo into target cells. Our previous results indicate that tissues including the placenta secrete lower levels of exosomes into blood under pathological conditions. We hypothesize that differential secretion of placental exosomes and expression of exosome contents will reflect the underlying physiology of spontaneous preterm birth (SPTB). We performed a case-control study comparing levels of placental exosomes in maternal plasma samples obtained following hospital admission from SPTB cases to term delivery and medically-indicated preterm delivery (MPTB)controls. Exosomes were isolated by ultracentrifugation, and nanoparticle analysis was performed to demonstrate that the majority of isolated microvesicles were in the size range consistent with exosomes. Western blots were performed utilizing antibodies against syncytin-1, a placenta-specific protein, and levels of placental exosomes were normalized to TSG-101 (an exosome marker) levels in the plasma samples (Figure 1). Levels of placental exosomes were measured in 16 SPTB cases (20-34 weeks), 10 MPTB (20-34 weeks), and 16 uncomplicated term delivery controls (38-39 weeks). Nanoparticle detection and electron microscopy showed that intact exosomes (range 40–100 nm) were enriched. Relative levels of placental exosomes (syncytin-1 label normalized to TSG 101) were similar in term delivery controls (established at 1.000) and MPTB (1.174+0.626) but were significantly lower in SPTB cases (0.493+0.205, P=0.036, Figure 2). Shedding of placental exosomes into maternal blood was lower in SPTB cases compared to term delivery and MPTB controls. It will be important to compare maternal plasma exosome levels earlier in pregnancy and the proteomic and RNA signatures in SPTB cases and term delivery controls. These studies have the potential to identify novel pathways by which the fetus contributes to the timing of birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Altered level of salivary placental growth factor is associated with preeclampsia

A pilot, case-control study was conducted to compare the concentrations of placental growth factor (PlGF) and placental alkaline phosphatase (PLAP) in saliva of preeclampsia (PE) patients with normotensive controls in the second and third trimesters. Measured by ELISA assays, levels of salivary PlGF were significantly lower in PE patients (n = 13) compared to controls (n = 15) (two-way ANOVA, p = 0.0208) independent of gestational age at time of collection (p = 0.49). Salivary PLAP differences between PE and controls were not statistically significant. Placenta-specific proteins are detectable in maternal saliva and may serve as noninvasive biomarkers to monitor placenta health and disease during pregnancy.

Placenta specific protein-1 in recurrent pregnancy loss and in In Vitro Fertilisation failure: a prospective observational case-control study

Observations from studies have provided evidence that Placenta-specific protein1 (PLAC1) is important for the establishment and maintenance of pregnancy and suggest it as a potential biomarker for gestational pathologies. The aim of this study is to investigate whether maternal serum PLAC1 levels have any impact on etiopathogenesis of recurrent pregnancy loss (RPL) and repeated implantation failure after In Vitro Fertilisation (RIF). We conducted a prospective observational case-control study in a Research Hospital. Twenty-eight patients with RPL (group 1), 30 patients with unexplained infertility and RIF (group 2), 29 fertile patients (group 3) were included. The demographic features and serum PLAC1 levels were compared. There was a significant difference in PLAC1 levels between the groups (group 1 = 19.71 + 16.55 ng/ml; group 2 = 4.82 + 1.44 ng/ml; group 3 = 0.89 + 0.62 ng/ml, respectively) (p=.001). Positive correlation was found between serum PLAC1 levels and abortion rates (r = 0.64; p=.001), a negative correlation was found between serum PLAC1 levels and live birth rates (r = −0.69; p=.001). PLAC1 might have a negative effect on implantation in RPL and RIF. There may be a subgroup of PLAC with different bioactivity. There are no relevant studies conducted among these populations, further large-scale studies are needed to assess the molecular role of PLAC1 on implantation.IMPACT STATEMENTWhat is already known about this subject? PLAC1 (placenta-specific protein-1) gene is located on the X chromosome which encodes for a protein that is thought to be important for placental development although its role has not been clearly defined. Studies in the literature have provided evidence that PLAC1 has an important role in the establishment and maintenance of pregnancy and suggest it as a potential biomarker for gestational pathologies. Several reports over the past few years have demonstrated PLAC1 expression in a variety of human tumours including lung cancers, breast cancer, hepatocellular and colorectal cancers, gastric cancers and uterine cancers.What do the results of this study add? There have been no previous studies conducted among patients with recurrent pregnancy loss (RPL) or repeated implantation failure after In Vitro Fertilisation (RIF) that have searched for any association between PLAC1 levels and implantation failure. This study has demonstrated higher PLAC1 levels in infertile women with RIF and RPL for the first time; suggesting that it could have a negative effect on implantation in these populations. PLAC1 could be detected in the serum as a biomarker that is associated with RIF and RPL. What are the implications of these findings for clinical practice and/or further research? Defining the precise role of PLAC1 during implantation will provide new insight into understanding of poor reproductive outcomes such as RIF and RPL and help in developing treatment strategies. Further large-scale studies with more patients are needed to uncover the clinical value of PLAC1 as a biomarker to predict repeated implantation failure and RPL.

Placenta-specific protein 8 promotes the proliferation of lung adenocarcinoma PC-9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway.

Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated the effect of PLAC8 on the proliferation of lung adenocarcinoma PC-9 cells and their sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It was found that the inhibition of PLAC8 expression in PC-9 cells resulted in significantly decreased proliferation, whereas overexpression of PLAC8 significantly increased the proliferation (P<0.05) of PC-9 cells. Furthermore, inhibition of PLAC8 expression resulted in decreased activity of the ERK signaling pathway, while PLAC8 overexpression increased activity of this pathway. Inhibition of the ERK signaling pathway with U0126 reversed the effects induced by inhibiting or overexpressing PLAC8 on cell proliferation. In addition, overexpression of PLAC8 significantly decreased the sensitivity of PC-9 cells to gefitinib, and this effect was reversed by U0126. Overall, these results suggest that PLAC8 is involved in the regulation of proliferation of lung adenocarcinoma PC-9 cells and impacts their sensitivity to an EGFR-TKI. Thus, PLAC8 is a potential novel target in lung adenocarcinoma for future studies.

PLAC8 overexpression correlates with PD-L1 upregulation and acquired resistance to chemotherapies in gallbladder carcinoma

Gallbladder carcinoma (GBC) is always diagnosed at an advanced stage, and patients often miss the opportunity for surgery. Gemcitabine (GEM) and platinum-based drugs, including oxaliplatin (OXA), are mainstays of chemotherapy. However, drug resistance causes treatment failure. Hence, salvage mechanisms are critical to improve outcomes. This study revealed the positive correlation between placenta-specific protein 8 (PLAC8) overexpression and PD-L1 overexpression in GBC. Given the roles of PLAC8 and PD-L1 in chemotherapy resistance, GEM-resistant and OXA-resistant cell lines (SGC966GR and SGC966OR, respectively) were established to test whether and how PLAC8 and PD-L1 function in chemotherapy resistance. Drug-insensitive SGC966GR and SGC966OR cells upregulated MRP and MDR1 and had high expression of PLAC8. PLAC8 blockade using siRNA reversed chemotherapy resistance and downregulated MRP and MDR1 in SGC966GR and SGC966OR cells, suggesting that PLAC8 mediates chemotherapy resistance in GBC. Consistent with the increased mRNA levels of PD-L1 after the acquisition of resistance, PLAC8 knockdown reduced PD-L1 mRNA expression in SGC966GR and SGC966OR cells. In conclusion, PLAC8 overexpression in GBC patients positively correlated with PD-L1 expression. PLAC8 conferred resistance to GEM and OXA by upregulating PD-L1 expression, and PLAC8 or PD-L1 blockade may have potential for overcoming chemotherapy resistance, providing therapeutic options for chemotherapy-refractory GBC patients.

Is the placental proteome impaired in well-controlled gestational diabetes?

In pregnancy complicated by gestational diabetes mellitus (GDM), the human placenta shows several pathological functional and structural changes, but the extent to which maternal glycemic control contributes to placental abnormalities remains unclear. The aim of this study was to profile and compare the proteome of placentas from healthy pregnant women and those with GDM, to investigate the placenta-specific protein composition and possible changes of its function in presence of GDM. Quantitative proteomic analysis, based on LC-MSE approach, revealed that higher (approximately 15% increase) levels of galectin 1 and collagen alpha-1 XIV chain (although the difference regarding the latter was at the limit of significance) were present in GDM samples, while heat shock 70kDa protein 1A/1B was less abundant in GDM placental tissue. These data seem to indicate that GDM, when well controlled, did not markedly affect the placental proteome.

Laeverin protein expression in normal and preeclamptic placentas using tissue microarray analysis

Laeverin is a placenta-specific protein that is normally expressed in the plasma membrane of human trophoblasts. In previous studies, we showed higher expression levels of laeverin gene in preeclamptic compared with normal placentas and found that laeverin protein was ectopically expressed in the cytoplasm of the preeclamptic placentas. Our objective was to investigate laeverin protein expression in normal and preeclamptic placentas combining immunohistochemistry and immunofluorescence. Tissue microarray analysis of 72 placentas, obtained from 33 preeclamptic and 39 uncomplicated pregnancies, was performed. Laeverin was labeled with a specific antibody for immunohistochemistry and immunofluorescence studies. Immunohistochemistry showed that laeverin was expressed in syncytiotrophoblasts, cytotrophoblasts and extravillous trophoblasts in all placentas examined. In preeclamptic placentas (n = 33) compared with normal placentas (n = 39), laeverin was expressed in the cell membrane in 21 (64%) vs. 21 (54%) samples (p = 0.726), in the cytoplasm in 3 (9%) vs. 2 (5%) samples (p = 0.795) and in both the cytoplasm and membrane in 9 (27%) vs. 16 (41%) samples (p = 0.0522). All placental samples that showed cytoplasmic expression of laeverin were obtained from women who delivered before 34 weeks of gestation (early-onset preeclampsia). Further, immunofluorescence studies showed laeverin expression in the cytoplasm of six preeclamptic (three early-onset and three late-onset) and one normal placenta but did not reveal any simultaneous cell membrane and cytoplasmic expression of laeverin. Laeverin is expressed in all trophoblast cell types of normal and preeclamptic placentas. Expression pattern of laeverin in trophoblast cells is heterogeneous and not necessarily membrane-bound.

PLAC8, a new marker for human interstitial extravillous trophoblast cells, promotes their invasion and migration.

ABSTRACTProper differentiation of trophoblast cells in the human placenta is a prerequisite for a successful pregnancy, and dysregulation of this process may lead to malignant pregnancy outcomes, such as preeclampsia. Finding specific markers for different types of trophoblast cells is essential for understanding trophoblast differentiation. Here, we report that placenta-specific protein 8 (PLAC8) is specifically expressed in the interstitial extravillous trophoblast cells (iEVTs) on the fetomaternal interface. Using model systems, including placental villi-decidua co-culture, iEVTs induction by using primary trophoblast cells or explants, etc., we found that PLAC8 promotes invasion and migration of iEVTs. Mechanistically, time-lapse imaging, GTPase activity assay, co-immunoprecipitation and RNA-seq studies show that PLAC8 increases the Cdc42 and Rac1 activities, and further induces the formation of filopodia at the leading edge of the migratory trophoblast cells. More interestingly, PLAC8 is significantly upregulated under hypoxia and expression of PLAC8 is higher in iEVTs from preeclamptic placentas when compared with those from the normal control placentas. Together, PLAC8 is a new marker for iEVTs and plays an important role in promoting trophoblast invasion and migration.

Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer.

Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis.

Placenta-specific protein 1 (PLAC1) expression in serous ovarian cancer is significantly determined by p53 mutation status

Placenta-specific protein 1 (PLAC1) expression in serous ovarian cancer is significantly determined by p53 mutation status

Placenta-specific protein 1 (PLAC1) expression regulated by TP53 in gynecologic cancer cell lines

Placenta-specific protein 1 (PLAC1) expression regulated by TP53 in gynecologic cancer cell lines

Placenta-Specific Protein 1 Expression in Human Papillomavirus 16/18-Positive Cervical Cancers Is Associated With Tumor Histology.

Expression of the trophoblast-specific gene placenta-specific protein 1 (PLAC1) has been detected in a wide variety of cancers. However, to date, PLAC1 expression has not been shown in cervical cancer. We have carried out a preliminary study that shows for the first time that PLAC1 is expressed in cervical cancers. A total of 16 primary cervical tumors were obtained from patients shown to be human papillomavirus (HPV) 16/18 positive. Total cellular RNA, genomic DNA, and total protein were purified from each tumor. These materials were then used to determine PLAC1 expression, TP53 mutation status, and p53 expression. The PLAC1 expression was demonstrated in all 16 primary cervical tumors. The highest levels of expression were found in the more aggressive squamous and adenosquamous histologic types compared with adenocarcinomas. Moreover, the proportion of total PLAC1 message coming from the P1 promoter, also termed the distal or cancer promoter, was significantly greater in the more aggressive squamous and adenosquamous histologic types compared with adenocarcinomas. Finally, in spite of all 16 tumors being HPV-16/18 positive, 3 of 8 squamous cell cancers and 2 of 5 adenocarcinomas expressed wild-type p53 protein. Consistent with the recently shown suppression of the PLAC1P1 promoter by wild-type p53, these p53 positive tumors displayed among the lowest P1-specific PLAC1 expression levels. The PLAC1 expression has been demonstrated for the first time in cervical cancers. This preliminary study has further revealed a complex relationship between PLAC1 expression, cervical cancer histologic type, p53, and HPV type that requires further investigation.

P53 mutation status is a primary determinant of placenta-specific protein 1 expression in serous ovarian cancers.

Placenta-specific protein 1 (PLAC1) expression is co-opted in numerous human cancers. As a consequence of PLAC1 expression, tumor cells exhibit enhanced proliferation and invasiveness. This characteristic is associated with increased aggressiveness and worse patient outcomes. Recently, the presence of the tumor suppressor p53 was shown in vitro to inhibit PLAC1 transcription by compromising the P1, or distal/cancer, promoter. We sought to determine if this phenomenon occurs in primary patient tumors as well. Furthermore, we wanted to know if p53 mutation influenced PLAC1 expression as compared with wild-type. We chose to study serous ovarian tumors as they are well known to have a high rate of p53 mutation. We report herein that the phenomenon of PLAC1 transcription repression does occur in serous ovarian carcinomas but only when TP53 is wild-type. We find that mutant or absent p53 protein de-represses PLAC1 transcription. We further propose that the inability of mutant p53 to repress PLAC1 transcription is due to the fact that the altered TP53 protein is unable to occupy a putative p53 binding site in the PLAC1 P1 promoter thus allowing transcription to occur. Finally, we show that PLAC1 transcript number is significantly negatively correlated with patient survival in our samples. Thus, we suggest that characterizing tumors for TP53 mutation status, p53 protein status and PLAC1 transcription could be used to predict likely prognosis and inform treatment options in patients diagnosed with serous ovarian cancer.

Identification and characterization of a novel multifunctional placenta specific protein 8 in Dugesia japonica

Placenta specific protein 8 (Plac8) has been well studied in vertebrates, yet little is known in invertebrates. In this study, a novel Plac8 from the planarian Dugesia japonica was identified and its functions in immune responses and development were characterized. Our results show that Djplac8 was expressed in the pharynx, epidermis and intestine of intact adult planarian. The expression of DjPlac8 increased significantly upon lipopolysaccharide (LPS) challenge, and inhibited the growth of the Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), suggesting the role of Plac8 in immune response. Spatial and temporal expression and distribution of DjPlac8 mRNA in regenerated planarians indicates that DjPlac8 was mainly expressed in the pharynx. In situ hybridization also revealed the elevated expression of the DjPlac8 gene in the embryonic pharynx, germ band and parenchyma cells, indicating an important role in embryonic development of D. japonica. When DjPlac8 was deactivated by RNA interference-mediated knockdown, the head of planarians underwent abnormal development. In summary, we identified DjPlac8 as a novel multifunctional protein that plays essential roles in immune response and development of planarians.

Oncogenic function of Plac1 on the proliferation and metastasis in hepatocellular carcinoma cells.

Placenta-specific protein 1 (Plac1), which is selectively expressed in the placental syncytiotrophoblast in adult normal tissues, plays an essential role in normal placental and embryonic development. Accumulating evidence suggests that enhanced Plac1 expression is closely associated with the progression of human cancer. Whether Plac1 contributes to the pathophysiology of hepatocellular carcinoma (HCC) remains unclear. In the present study, our data revealed that the expression of Plac1 in human HCC tissues was upregulated, which significantly correlated with metastasis of HCC. Knockdown of Plac1 by small interfering RNA (siRNA) in Bel-7402 and HepG2 cells resulted in decreasing tumor cell proliferation and increasing apoptosis, which implied the oncogenic potential of Plac1. Moreover, silencing of Plac1 induced G1 cell cycle arrest through suppression of cyclinD1 and CDK4 expression. Furthermore, depletion of Plac1 repressed epithelial-mesenchymal transition (EMT), with decreased cell migration and invasion, supporting upregulated E-cadherin expression and downregulated vimentin, twist and snail expression that characterize EMT. Further study suggested that decreased Plac1 expression attenuated the phosphorylation of Akt. These findings have uncovered that Plac1 plays a pivotal role in the progression of HCC, and may serve as a novel therapeutic target for HCC.

Disorders in barrier protein mRNA expression and placenta secretory activity under the influence of polychlorinated biphenyls in vitro

Pregnancy disorders are often correlated with the presence of organic pollutants in the tissues of living bodies. The aim of this study was to investigate the effects (over 24 and 48 hours) of polychlorinated biphenyls (PCBs) 153, 126, and 77 at doses of 1, 10, and 100 ng/mL on barrier function and secretory activity in cow placentome sections collected during the second trimester of pregnancy. None of the PCBs affected the viability of the sections (P > 0.05). Polychlorinated biphenyl 153 decreased (P < 0.05) connexin 26 (Cx 26) mRNA expression, and all three PCBs reduced (P < 0.05) Cx 43 mRNA expression. Cx 32 mRNA expression showed a downward trend (P > 0.05) under the influence of PCBs 126 and 77. Moreover, PCBs 153 and 126 increased keratin 8 (KRT8) mRNA expression, whereas all PCBs decreased (P < 0.05) placenta specific protein 1 (PLAC-1) mRNA expression without changing (P > 0.05) hypoxia inducible factor 1α (HIF1α) mRNA expression. Concomitantly, PCBs 153 and 126 stimulated (P < 0.05) cyclooxygenase 2 (COX-2) mRNA expression, all PCBs increased (P < 0.05) prostaglandin E2 synthase (PGES) mRNA expression, and PCBs 126 and 77 increased prostaglandin E2 (PGE2) secretion. All three PCBs decreased (P < 0.05) prostaglandin F2α synthase (PGFS) mRNA expression and prostaglandin F2α (PGF2α) secretion. In addition, all three PCBs increased (P < 0.05) neurophysin I/oxytocin (NP-I/OT) mRNA expression and OT secretion but did not affect peptidyl-glycine-α-amidating monooxygenase (PGA) mRNA expression (P > 0.05). Moreover, the PCBs increased (P < 0.05) estradiol (E2) secretion, whereas progesterone (P4) secretion remained unchanged (P > 0.05). These changes could affect trophoblast invasion and uterine contractility and thus impact the course of gestation and/or fetal development in the cow.

PLAC1 is involved in human trophoblast syncytialization

Placenta specific protein 1 (PLAC1) is thought to be important for murine and human placentation because of its abundant expression in placenta; however, the trophoblast subtypes that express PLAC1 at the fetomaternal interface and the major role of PLAC1 in placentation are still unclear. This study investigated the expression pattern of PLAC1 at the human fetomaternal interface and its involvement in trophoblast syncytialization. Localization of PLAC1 at the fetomaternal interface was studied using in situ hybridization (ISH) and immunohistochemistry (IHC) assays. Real time RT-PCR and Western Blot were employed to exhibit the expression pattern of PLAC1 during human spontaneous syncytialization of term primary cytotrophoblast cells (CTBs). Spontaneous syncytialization of a primary term CTBs model transfected with siRNA specific to PLAC1 was used to investigate the role of PLAC1 during human trophoblast syncytialization. The results showed that PLAC1 was mainly expressed in the human villous syncytiotrophoblast (STB) layer throughout gestation, and the expression level of PLAC1 was significantly elevated during human trophoblast syncytialization. Down-regulation of PLAC1 via specific PLAC1 siRNA transfection attenuated spontaneous syncytialization of primary term CTBs (p<0.05) as indicated by cell fusion index and the expression patterns of the corresponding markers. These data demonstrate the facilitative role of PLAC1 in normal human trophoblast syncytialization.