the trophoblast model of cancer

Preeclampsia (PE) is a pregnancy-related disorder that is a leading cause of maternal death. The failure of spiral artery remodeling due to insufficient trophoblast migration and invasion is critical in the pathogenesis of PE. Recently, the CC motif chemokine ligand 21 (CCL21) has been widely linked to cancer cell invasion and migration. However, their potential mechanisms are still unknown. In this study, we found that CCL21 expression was significantly lower in the PE group than that in the control group...

We aimed to evaluate the expression of YAP1, PTEN, VEGF in the placentas of patients with preeclampsia and placentas of healthy pregnant women for trophoblast invasion, which is similar to cancer etiopathogenesis. The placentas of 70 women who gave birth, including 30 preeclampsia and 40 healthy controls, were evaluated. YAP1, PTEN and VEGF immunohistochemical staining were performed using the microarray method on placental tissue. The mean ± standard deviation for YAP1, PTEN and VEGF intensity were; 1...

P-glycoprotein (P-gp, encoded by the ABCB1) and breast cancer resistance protein (BCRP/ABCG2) are efflux multidrug resistance (MDR) transporters localized at the syncytiotrophoblast barrier of the placenta and protect the conceptus from drug and toxin exposure throughout pregnancy. Infection is an important modulator of MDR expression and function. This review comprehensively examines the effect of infection on the MDR transporters, P-gp and BCRP in the placenta. Infection PAMPs such as bacterial lipopolysaccharide (LPS) and viral polyinosinic-polycytidylic acid (poly I:C) and single-stranded (ss)RNA, as well as infection with Zika virus (ZIKV), Plasmodium berghei ANKA (modeling malaria in pregnancy - MiP) and polymicrobial infection of intrauterine tissues (chorioamnionitis) all modulate placental P-gp and BCRP at the levels of mRNA, protein and or function; with specific responses varying according to gestational age, trophoblast type and species (human vs...

Gestational Trophoblastic Neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and Multi-layer Perceptron (MLP) modelling (n=4,191) generated six models (M1-6)...

Gestational diabetes mellitus (GDM) is an increasingly frequent disease occurred during pregnancy. HOXC8 has been disclosed to take part in the regulation of cancers. Additionally, the HOXC8 expression was dramatically decreased in the placenta of pre-eclampsia patients, but its expression and function have not been investigated in GDM. In this work, it was demonstrated that the mRNA and protein expression of HOXC8 was lower in GDM placenta tissues and GDM cell model. In addition, HOXC8 facilitated trophoblast cell proliferation and weakened trophoblast cell mitochondrial apoptosis...

INTRODUCTION: The Trophoblast cell surface antigen 2 (TROP2) is expressed in many carcinomas and may represent a target for treatment. Sacituzumab govitecan (SG) is a TROP2-directed antibody-drug conjugate (ADC). Nearly nothing is known about the biological effectiveness of SG in esophageal adenocarcinoma (EAC). MATERIAL AND METHODS: We determined the TROP2 expression in nearly 600 human EAC. In addition, we used the EAC cell lines (ESO-26, OACM5.1C, and FLO-1) and a xenograft mouse model to investigate this relationship...

Multiple parallels exist between placentation and cancer dissemination at molecular, cellular, and anatomical levels, presenting placentation as a unique model to mechanistically understand the onset of cancer metastasis. In humans, interaction of placenta and the endometrium results eventually in deep invasion of placental extravillous trophoblasts (EVTs) into the maternal stroma, a process similar to stromal trespass by disseminating carcinoma cells. In anticipation of implantation, endometrial fibroblasts (ESFs) undergo a process called decidualization during the secretory phase of the menstrual cycle...

BACKGROUND: Choriocarcinoma is a rare and aggressive gynecological malignancy. The standard treatment is systemic chemotherapy as choriocarcinoma exhibits high chemosensitivity. However, refractory choriocarcinoma exhibits chemoresistance; thus, the prognosis remains very poor. This study aimed to identify novel therapeutic agents for choriocarcinoma by utilizing a drug repositioning strategy. METHODS: Three choriocarcinoma cell lines (JAR, JEG-3, and BeWo) and a human extravillous trophoblast cell line (HTR-8/SVneo) were used for the analyses...

Trophoblastic cell surface antigen 2 (TROP2) is a membrane glycoprotein overexpressed in many solid tumors with a poor prognosis, including intestinal neoplasms. In our study, we show that TROP2 is expressed in preneoplastic lesions, and its expression is maintained in most colorectal cancers (CRC). High TROP2 positivity correlated with lymph node metastases and poor tumor differentiation and was a negative prognostic factor. To investigate the role of TROP2 in intestinal tumors, we analyzed two mouse models with conditional disruption of the adenomatous polyposis coli ( Apc ) tumor-suppressor gene, human adenocarcinoma samples, patient-derived organoids, and TROP2-deficient tumor cells...

A problem in developmental toxicology is the massive loss of life from fertilization through gastrulation, and the surprising lack of knowledge of causes of miscarriage. Half to two-thirds of embryos are lost, and environmental and genetic causes are nearly equal. Simply put, it can be inferred that this is a difficult period for normal embryos, but that environmental stresses may cause homeostatic responses that move from adaptive to maladaptive with increasing exposures. At the lower 50% estimate, miscarriage causes greater loss-of-life than all cancers combined or of all cardio- and cerebral-vascular accidents combined...

In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients. NanoString gene expression and ChIP analysis confirmed trophoblast cell surface antigen 2 (TROP2) as a novel inhibitory ATF2 target gene. This inverse correlation was further observed in primary human tumor tissues...

PURPOSE: Trophoblast Cell Surface Antigen 2 (TROP2) is a glycoprotein expressed in many cancers. A TROP2 antibody-drug conjugate (ADC) was effective in metastatic triple-negative breast cancer (TNBC). We studied TROP2 gene (TACSTD2) expression and associations with tumor and clinical characteristics, as well as selected external genes in primary breast cancer. METHODS: TACSTD2 gene expression was evaluated using microarray data from I-SPY 1 (n = 149), METABRIC (n = 1992), and TCGA (n = 817)...

Advances in Artificial Reproductive Technologies (ARTs) in bovine embryos to produce cloned pregnancies have been developed in the last years, however high pregnancy losses rates still present. Those rates are associated to placental morphology alterations that are majorly focused on extracellular matrix (ECM) alterations and consequently placentome hyperplasia, increased trophoblast cell migration and vascular defects. Herein, we aimed to search, at protein level, pathways altered by ART that can modify the placental development harmony...

The heterogeneity of cancer cells, in part maintained via the expression of multiple isoforms, introduces significant challenges in designing effective therapeutic approaches. In this regard, isoforms of the immune checkpoint HLA-G have been found in most of the tumors analyzed, such as ccRCC, the most common human renal malignancy. In particular, HLA-G∆α1, which is the only HLA-G isoform described that lacks the α1 extracellular domain, has been newly identified in ccRCC and now here in trophoblasts. Using a cellular model expressing HLA-G∆α1, we have uncovered its specific and overlapping functional roles, relative to the main HLA-G isoform, i...

INTRODUCTION: Triple-negative breast cancer (TNBC) is the most fatal molecular subtype of breast cancer because of its aggressiveness and resistance to chemotherapy. FDA-approved therapies for TNBC are limited to poly(ADP-ribose) polymerase inhibitors, immune checkpoint inhibitors, and trophoblast cell surface antigen 2-targeted antibody-drug conjugate. Therefore, developing a novel effective targeted therapy for TNBC is an urgent unmet need. AREAS COVERED: In this narrative review, we discuss emerging targets for TNBC treatment discovered in early translational studies...

Embryonic development involves orchestrated events regulated by a plethora of factors. Epigenetic regulation is one such key aspect regulating embryonic development. We are investigating the role played by Aprataxin and PNK-like factor (APLF), a histone chaperone, in regulating cellular transitions in the context of embryonic development. APLF is documented as a DNA damage-specific histone chaperone and has already been studied in our lab in the context of the generation of induced pluripotent stem cells and breast cancer metastasis as a regulator of epithelial to mesenchymal transition...

Patient registries linked to biorepositories constitute a valuable asset for clinical and translational research in oncology. The Spanish Group of Ovarian Cancer Research (GEICO), in collaboration with the Spanish Biobank Network (RNBB), has developed a multicentre, multistakeholder, prospective virtual clinical registry (VCR) associated with biobanks for the collection of real-world data and biological samples of gynaecological cancer patients. This collaborative project aims to promote research by providing broad access to high-quality clinical data and biospecimens for future research according to the needs of investigators and to increase diagnostic and therapeutic opportunities for gynaecological cancer patients in Spain...

BACKGROUND: Embryo implantation into the uterus is a crucial step for human reproduction. A hypothesis has been proposed that the molecular circuit invented by trophoblasts for invasive embryo implantation during evolution might be misused by cancer cells to promote malignancy. Unfortunately, our current understanding of the molecular mechanism underlying embryo implantation is far from complete. RESULTS: Here we used the mouse as an animal model and generated a single-cell transcriptomic atlas of the embryo implantation site of mouse uterus at the invasion phase of embryo implantation on gestational day 6...

KiSS-1, first identified as an anti-metastasis gene in melanoma, encodes C-terminally amidated peptide products, including kisspeptin-145, kisspeptin-54, kisspeptin-14, kisspeptin-13 and kisspeptin-10. These products are endogenous ligands coupled to G protein-coupled receptor 54 (GPR54)/hOT7T175/AXOR12. To date, the regulatory activities of the KiSS-1/GPR54 system, such as puberty initiation, antitumor metastasis, fertility in adulthood, hypothalamic-pituitary-gonadal axis (HPG axis) feedback, and trophoblast invasion, have been investigated intensively...

Metabolic reprogramming could promote cellular adaptation in response to chemotherapeutic drugs in cancer cells. Herein, we aimed to characterize the metabolomic profiles regulated by Dipeptidyl Peptidase 4 (DPP4) in methotrexate (MTX)-resistant gestational trophoblastic neoplastic (GTN) cells. A total of eighty metabolites were found to be commonly altered in DPP4-depleted JAR/MTX and JEG3/MTX cells. Cholesterol biosynthesis-related metabolites were markedly impacted by DPP4 knockdown in MTX-resistant sublines...