Interleukin 11: similar or opposite roles in female reproduction and reproductive cancer?

2016 ◽  
Vol 28 (4) ◽  
pp. 395 ◽  
Author(s):  
Amy Winship ◽  
Ellen Menkhorst ◽  
Michelle Van Sinderen ◽  
Evdokia Dimitriadis
Keyword(s):  
Embryo Implantation ◽  
Cell Types ◽  
Malignant Cell ◽  
Vascular Supply ◽  
Female Reproduction ◽  
Placental Development ◽  
Invasion And Migration ◽  
Gynaecological Malignancy ◽  
Uterine Environment ◽  
And Migration

During placental development and carcinogenesis, cell invasion and migration are critical events in establishing a self-supporting vascular supply. Interleukin (IL)-11 is a pleiotropic cytokine that affects the invasive and migratory capabilities of trophoblast cells that form the placenta during pregnancy, as well as various malignant cell types. The endometrium is the site of embryo implantation during pregnancy; conversely, endometrial carcinoma is the most common gynaecological malignancy. Here, we review what is known about the role of IL-11 in trophoblast function and in gynaecological malignancies, focusing primarily on the context of the uterine environment.

scholarly journals The Role of LIN28-let-7-ARID3B Pathway in Placental Development

2020 ◽  
Vol 21 (10) ◽  
pp. 3637 ◽  
Author(s):  
Asghar Ali ◽  
Gerrit J. Bouma ◽  
Russell V. Anthony ◽  
Quinton A. Winger
Keyword(s):  
Embryo Implantation ◽  
Trophoblast Cells ◽  
Placental Development ◽  
Proliferating Cells ◽  
Interaction Domain ◽  
Invasion And Migration ◽  
Reduce Cell Proliferation ◽  
High Let ◽  
And Migration

Placental disorders are a major cause of pregnancy loss in humans, and 40–60% of embryos are lost between fertilization and birth. Successful embryo implantation and placental development requires rapid proliferation, invasion, and migration of trophoblast cells. In recent years, microRNAs (miRNAs) have emerged as key regulators of molecular pathways involved in trophoblast function. A miRNA binds its target mRNA in the 3ʹ-untranslated region (3ʹ-UTR), causing its degradation or translational repression. Lethal-7 (let-7) miRNAs induce cell differentiation and reduce cell proliferation by targeting proliferation-associated genes. The oncoprotein LIN28 represses the biogenesis of mature let-7 miRNAs. Proliferating cells have high LIN28 and low let-7 miRNAs, whereas differentiating cells have low LIN28 and high let-7 miRNAs. In placenta, low LIN28 and high let-7 miRNAs can lead to reduced proliferation of trophoblast cells, resulting in abnormal placental development. In trophoblast cells, let-7 miRNAs reduce the expression of proliferation factors either directly by binding their mRNA in 3ʹ-UTR or indirectly by targeting the AT-rich interaction domain (ARID)3B complex, a transcription-activating complex comprised of ARID3A, ARID3B, and histone demethylase 4C (KDM4C). In this review, we discuss regulation of trophoblast function by miRNAs, focusing on the role of LIN28-let-7-ARID3B pathway in placental development.

Id-2 regulates critical aspects of human cytotrophoblast differentiation, invasion and migration

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 549-558 ◽  
Author(s):  
M.J. Janatpour ◽  
M.T. McMaster ◽  
O. Genbacev ◽  
Y. Zhou ◽  
J. Dong ◽  
...  
Keyword(s):  
Dna Binding ◽  
Adenovirus Vector ◽  
Bhlh Transcription Factor ◽  
Placental Development ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Hypoxic Conditions ◽  
Bhlh Factors ◽  
Cytotrophoblast Cells ◽  
And Migration

During early human placental development, the conceptus attaches itself to the uterus through cytotrophoblast invasion. Invasive cytotrophoblast cells differentiate from precursor villous cytotrophoblasts, but the essential regulating factors in this process are unknown. Basic helix-loop-helix (bHLH) transcription factor dimers are essential regulators of mouse trophoblast development. We therefore examined the importance of this family of factors in the human placenta. In many cell lineages, bHLH factors are sequestered by members of the Id family, HLH proteins that lack the basic DNA binding domain (Inhibitor of DNA binding proteins (Id-1 to Id-4)). During differentiation of some tissues, Id expression declines, allowing bHLH factors to dimerize, bind DNA and trans-activate lineage-specific genes. To begin to study the role of bHLH transcription factors in human placental development, we first characterized Id expression in cytotrophoblast cells. The cells expressed Id-3 constitutively; Id-2 was downregulated, at the mRNA and protein levels, as the cells differentiated in culture and in situ, respectively. In cases when cytotrophoblast differentiation was compromised (in placentas from women with preeclampsia, or in cells grown under hypoxic conditions in culture), Id-2 expression was maintained. To assess the functional relevance of these correlations, we used an adenovirus vector to maintain Id-2 protein expression in cultured cytotrophoblasts. Compared to control (lacZ-expressing) cells, cytotrophoblasts transduced to constitutively express Id-2 retained characteristics of undifferentiated cells: (alpha)1 integrin expression was low and cyclin B expression was retained. Furthermore, invasion through Matrigel was partially inhibited and migration was strikingly enhanced in Id-2-expressing cells. These results suggest that Id-2 and the bHLH factors that it partners play important roles in human cytotrophoblast development.

scholarly journals LIN28B regulates transcription and potentiates MYCN-induced neuroblastoma through binding to ZNF143 at target gene promotors

2020 ◽  
Vol 117 (28) ◽  
pp. 16516-16526 ◽  
Author(s):  
Ting Tao ◽  
Hui Shi ◽  
Luca Mariani ◽  
Brian J. Abraham ◽  
Adam D. Durbin ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Distant Metastases ◽  
Malignant Cell ◽  
Gene Promoters ◽  
Invasion And Migration ◽  
Protein Protein Interaction ◽  
Cell Adhesion And Migration ◽  
And Migration

LIN28B is highly expressed in neuroblastoma and promotes tumorigenesis, at least, in part, through inhibition oflet-7microRNA biogenesis. Here, we report that overexpression of either wild-type (WT) LIN28B or a LIN28B mutant that is unable to inhibitlet-7processing increases the penetrance of MYCN-induced neuroblastoma, potentiates the invasion and migration of transformed sympathetic neuroblasts, and drives distant metastases in vivo. Genome-wide chromatin immunoprecipitation coupled with massively parallel DNA sequencing (ChIP-seq) and coimmunoprecipitation experiments show that LIN28B binds active gene promoters in neuroblastoma cells through protein–protein interaction with the sequence-specific zinc-finger transcription factor ZNF143 and activates the expression of downstream targets, including transcription factors forming the adrenergic core regulatory circuitry that controls the malignant cell state in neuroblastoma as well asGSK3BandL1CAMthat are involved in neuronal cell adhesion and migration. These findings reveal an unexpectedlet-7–independent function of LIN28B in transcriptional regulation during neuroblastoma pathogenesis.

Antineoplastic Effects of NF-κB Inhibition by DHMEQ (Dehydroxymethylepoxyquinomicin) Alone and in Co-treatment with Radio-and Chemotherapy in Medulloblastoma Cell Lines

2018 ◽  
Vol 18 (4) ◽  
pp. 541-549 ◽  
Author(s):  
Priscila M.M. Ramos ◽  
Julia A. Pezuk ◽  
Angel M. Castro-Gamero ◽  
Harley F. Oliveira ◽  
Carlos A. Scrideli ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Invasion ◽  
Cell Types ◽  
Chemotherapeutic Agents ◽  
Anticancer Effect ◽  
Invasion And Migration ◽  
And Migration ◽  
Tumor Types ◽  
Medulloblastoma Cell Lines ◽  
Potential Antitumor

Background: NF-κB is a transcription factor involved in the transcriptional regulation of a large number of genes related to tumorigenesis in several cancer cell types, and its inhibition has been related to anticancer effect. DHMEQ (Dehydroxymethylepoxyquinomicin) is a compound that blocks the translocation of NF-κB from the cytoplasm to the nucleus, thus inhibiting its activity as a transcriptional activator. Several studies have shown the antineoplastic effects of DHMEQ in numerous tumor types, however, there are no surveys that tested their effects in MB. Objectives: The aim of the present study was to evaluate the effects of DHMEQ as NF-κB inhibitor in pediatric MB cell lines. Method: We used the UW402, UW473 and ONS-76 medulloblastoma (MB) cell lines to verify the effect of DHMEQ on proliferation, clonogenic capacity, apoptosis, cell invasion and migration, and evaluated the effect of the combination with other drugs and the potential as a radiosensitizator. Results: A significant decrease in the cell growth, a strong inhibition of the clonogenic capacity, migration and cell invasion was observed after NF-κB inhibition in the three MB cell lines. Conversely, increased level of apoptosis rates were demonstrated. Additionally, treatments with DHMEQ combined with other chemotherapeutic agents were synergic in most points, and a strong radiosensitization by this compound was observed in the three MB cell lines. Conclusion: DHMEQ has potential antitumor effect on MB cells, and it may be considered a new therapeutic agent to improve treatment approaches in MB.

Downregulation of aromatase plays a dual role in preeclampsia

2021 ◽  
Author(s):  
Dawei Zhu ◽  
Jie Huang ◽  
Xing Gu ◽  
Li Li ◽  
Jian Han
Keyword(s):  
Infant Health ◽  
Animal Experiments ◽  
Dual Role ◽  
Main Role ◽  
Placental Development ◽  
Serum Samples ◽  
Invasion And Migration ◽  
Maternal And Infant Health ◽  
Pregnant Mice ◽  
And Migration

Abstract Preeclampsia (PE) is a gestational disease which seriously impairs maternal and infant health. However, the pathogenesis of PE remains unclear. The aromatase (CYP19A1) in placenta converts androgens from maternal and fetal adrenal glands to estrogen. Therefore, this change in the aromatase expression or function and the subsequent change of steroids in the placenta could be related to the pathophysiology of PE. In this study, we first analysed the expression of CYP19A1 in clinical placental tissues as well as the level of sex hormones in corresponding serum samples. The results showed that the expression of aromatase in the placenta of PE patients was relatively low and accompanied by a sex hormone imbalance. Subsequently, animal experiments showed that ischemia and hypoxia lead to a low expression of CYP19A1, and that PE-like symptoms appear in pregnant mice following decreased or inhibited CYP19A1 expression. It was also found that, with the downregulation of CYP19A1 expression, the invasion and migration abilities of trophoblast cells were enhanced, which benefited placental implantation. However, alongside this, apoptosis and the inflammatory response were also increased, which was detrimental to placental development. Phosphoproteomic analyses revealed that the activation of the PI3K/AKT signaling pathway may play a key role in these processes. In conclusion, the downregulation of aromatase has a dual role in PE, among which the induction of the disease is the main role. Our study provides a potential novel method for the early prediction and treatment of PE.

scholarly journals The Involvement of Exosomes in Glioblastoma Development, Diagnosis, Prognosis, and Treatment

2020 ◽  
Vol 10 (8) ◽  
pp. 553 ◽  
Author(s):  
Adrian Bălașa ◽  
Georgiana Șerban ◽  
Rareş Chinezu ◽  
Corina Hurghiș ◽  
Flaviu Tămaș ◽  
...  
Keyword(s):  
Vascular Supply ◽  
Early Management ◽  
New Era ◽  
Invasion And Migration ◽  
Tumour Cell Invasion ◽  
Invasive Capacity ◽  
Induce Resistance ◽  
And Migration ◽  
Postsurgical Recurrence ◽  
Molecular Manipulation

Brain tumours are a serious concern among both physicians and patients. The most feared brain tumour is glioblastoma (GBM) due to its heterogeneous histology, substantial invasive capacity, and rapid postsurgical recurrence. Even in cases of early management consisting of surgery, chemo-, and radiotherapy, the prognosis is still poor, with an extremely short survival period. Consequently, researchers are trying to better understand the underlying pathways involved in GBM development in order to establish a more personalised approach. The latest focus is on molecular characterisation of the tumour, including analysis of extracellular vesicles (EVs), nanostructures derived from both normal and pathological cells that have an important role in intercellular communication due to the various molecules they carry. There are two types of EV based on their biogenesis, but exosomes are of particular interest in GBM. Recent studies have demonstrated that GBM cells release numerous exosomes whose cargo provides them the capacity to facilitate tumour cell invasion and migration, to stimulate malignant transformation of previously normal cells, to increase immune tolerance towards the tumour, to induce resistance to chemotherapy, and to enhance the GBM vascular supply. As exosomes are specific to their parental cells, their isolation would allow a deeper perspective on GBM pathogenesis. A new era of molecular manipulation has emerged, and exosomes are rapidly proving their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting GBM cells. Nonetheless, further research will be required before exosomes could be used in clinical practice. This review aims to describe the structural and functional characteristics of exosomes and their involvement in GBM development, diagnosis, prognosis and treatment.

Physiological Mechanisms of Tumor-Cell Invasion and Migration

Physiology ◽  
2005 ◽  
Vol 20 (3) ◽  
pp. 194-200 ◽  
Author(s):  
David H. Geho ◽  
Russell W. Bandle ◽  
Timothy Clair ◽  
Lance A. Liotta
Keyword(s):  
Tumor Invasion ◽  
Developmental Regulation ◽  
Cell Types ◽  
Tumor Cell Invasion ◽  
Physiological Mechanisms ◽  
Invasion And Migration ◽  
Extracellular Signaling ◽  
Multiple Cell ◽  
Pharmacological Blockade ◽  
And Migration

Recent advances in understanding the complex biology of the microenvironment that underlies tumor invasion and migration have revealed novel and promising therapeutic targets. Pharmacological blockade of intra- and extracellular signaling events that regulate migration and survival of multiple cell types may disrupt the host-tumor conspiracy that allows escape from normal developmental regulation.

Effect of id1 and id2 proteins (inhibitors of dna binding) expression in human colorectal cell lines

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22179-e22179
Author(s):  
B. Calvo ◽  
A. Muñoz ◽  
M. Jangi ◽  
U. Aresti ◽  
A. Garcia ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cell Lines ◽  
Critical Role ◽  
Malignant Cell ◽  
Migration And Invasion ◽  
Cell Phenotype ◽  
Invasion And Migration ◽  
Helix Loop Helix ◽  
Colorectal Cell ◽  
And Migration

e22179 Background: Id1 and Id2 proteins are negative regulators of basic helix-loop-helix transcription factors, a family of components in the transcriptional network regulating cell growth and differentiation. Id1 and Id2 are overexpressed in human colorectal carcinoma and might play a critical role in the malignant cell phenotype. Methods: Two cell-lines were use for the analysis. NCM460: immortal non-tumoral cells from colon mucosa, and Caco-2: epithelial cells from colorectal carcinoma. Cell-lines were transfected with different constructs based on pLXSN vector (Clontech) to overexpress or inhibit the expression of the Id1 and Id2 genes, and then cultured for the analysis. Quantification of Id1 and Id2 expression were assessed by RT-PCR and Western-blot, respectively. A gene expression profile using oligonucleotide microarrays (Agilent Technologies) was performed in each cell line. Results: NCM460 cells and Caco-2 cells overexpressing Id1 (NCM460-Id1 and Caco-2-Id1) showed a statistically significant higher proliferation, invasion and migration, compared with both normal and Id1 inhibited cells. Id2 overexpression was related with a higher invasion capability only in NCM460 cells, without significant effect on proliferation and migration. NCM460-Id1 cells showed overexpression of PTMA, TYMS and LMNB1 genes, whereas HOXB8, LRP1, MMP17, NDRG1, MAP3K10, SCGb3A1 and BBC3 were upregulated. PTP4A1 and DKK1 were overexpressed in Caco-2-Id1 cells, and NDRG1, LRP1, FMOD and ENO1 were repressed. Conclusions: Id-1 expression is associated with proliferation, migration and invasion in both normal and tumoral colonic cell lines, and it is related with regulation of several genes implicated in colorectal cancer phenotype. Id proteins might be a potential target for the development of new antineoplastic agents. No significant financial relationships to disclose.

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

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