Leukemia inhibitory factor triggers activation of signal transducer and activator of transcription 3, proliferation, invasiveness, and altered protease expression in choriocarcinoma cells

Fitzgerald, Justine S.; Tsareva, Svetlana A.; Poehlmann, Tobias G.; Berod, Luciana; Meißner, Anja; Corvinus, Florian; Wiederanders, Bernd; Pfitzner, Edith; Markert, Udo R.; Friedrich, Karlheinz

doi:10.1016/j.biocel.2005.02.025

Cited by 93 publications

(75 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also demonstrated that LIF induced phosphorylation of STAT3 in Hs-700T cells. Consistently, LIF activates STAT3 and enhances invasiveness by alteration of protease expression in choriocarcinoma cells (23). LIF has activated transcription factors, such as TRE3 and TFEB, which are activators of E-cadherin in renal carcinoma cells (24).…”

Section: Discussionmentioning

confidence: 90%

Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression

Kamohara¹,

Ogawa²,

Ishiko³

et al. 2007

Int J Oncol

View full text Add to dashboard Cite

Abstract. Leukemia inhibitory factor (LIF) is a pleiotrophic cytokine, which plays an important role in inducing cancer cachexia. We have previously reported that LIF promotes cell proliferation in some human carcinoma cells through c-fos, jun-B and cyclin-E expression. In the present study, we analyzed the regulation of LIF and its receptor (LIFR) expression in pancreatic carcinoma cells. Seven pancreatic carcinoma cells expressed constitutively LIF and its heterodimer receptor (LIFR and gp130) mRNA in RPMI-1640 medium without FBS. The amount of LIF immunoreactive protein was 132.5±52 pg/10 6 cells in culture supernatants without FBS. Pro-inflammatory cytokines, such as TNF-·, IL-1ß, IL-6, IL-8, or LIF, enhanced the expression of LIF mRNA in Hs-700T and Hs-766T cells. Addition of LIF significantly induced cell proliferation of Hs700T in 13 days LIF dose-dependently. However, anti-LIF IgG failed to suppress cell proliferation in Hs-700T cells. LIF acted as a paracrine growth factor in Hs-700T cells, which expressed low amount of LIF without stimuli. Cellular signal transductions by LIF was down-regulated by inhibitors of protein kinase C (PKC), protein tyrosine kinase (PTK), and Ca/Calmodulin. LIF induced phosphorylation of STAT3. Moreover, exogenous LIF upregulated the expression of LIFR mRNA. Antisense LIFR oligonucleotide significantly suppressed cell growth in the presence of LIF in Hs-700T cells. These results suggest that cytokine network might alter the expression and responsiveness to LIF in tumor microenvironment.

show abstract

Section: Discussionmentioning

confidence: 90%

Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression

Kamohara¹,

Ogawa²,

Ishiko³

et al. 2007

Int J Oncol

View full text Add to dashboard Cite

show abstract

“…Both matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), which inhibit the function of MMPs, are expressed in trophoblasts and decidual cells to regulate trophoblast migration and invasion (20). In addition, the STAT3 transcription factor is activated in the leukemia inhibitory factor (LIF) signaling pathway to promote trophoblast cell migration (16). Nevertheless, activation of STAT3 and overexpression of MMPs was also commonly found in invasive tumors of different tissue origins (17,35), suggesting that additional regulatory mechanisms specific to placenta may be involved in control of trophoblast migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

High-Temperature Requirement Protein A4 (HtrA4) Suppresses the Fusogenic Activity of Syncytin-1 and Promotes Trophoblast Invasion

Wang

Cheong

Lee

et al. 2012

Molecular and Cellular Biology

View full text Add to dashboard Cite

dCell-cell fusion and cell invasion are essential for placental development. Human cytotrophoblasts in the chorionic villi may undergo cell-cell fusion to form syncytiotrophoblasts to facilitate nutrient-gas exchange or differentiate into extravillous trophoblasts (EVTs) to facilitate maternal-fetal circulation. The placental transcription factor glial cells missing 1 (GCM1) regulates syncytin-1 and -2 expression to mediate trophoblast fusion. Interestingly, GCM1 and syncytin-1 are also expressed in EVTs with unknown physiological functions. In this study, we performed chromatin immunoprecipitation-on-chip (ChIP-chip) analysis and identified the gene for high-temperature requirement protein A4 (HtrA4) as a GCM1 target gene, which encodes a serine protease facilitating cleavage of fibronectin and invasion of placental cells. Importantly, HtrA4 is immunolocalized in EVTs at the maternal-fetal interface, and its expression is decreased by hypoxia and in preeclampsia, a pregnancy complication associated with placental hypoxia and shallow trophoblast invasion. We further demonstrate that HtrA4 interacts with syncytin-1 and suppresses cell-cell fusion. Therefore, HtrA4 may be crucial for EVT differentiation by playing a dual role in prevention of cellcell fusion of EVTs and promotion of their invasion into the uterus. Our study reveals a novel function of GCM1 and HtrA4 in regulation of trophoblast invasion and that abnormal HrtA4 expression may contribute to shallow trophoblast invasion in preeclampsia.H uman placentation proceeds fast after embryo implantation, and different classes of specialized trophoblast cells have evolved to establish blood circulation for nutrient, gas, and waste exchange between mother and fetus. In brief, the mononuclear cytotrophoblasts in chorionic villi proliferate and differentiate through cell-cell fusion into a multinucleated syncytiotrophoblast layer, which is in direct contact with maternal blood to mediate the above-mentioned exchanges and produce hormones and growth factors for pregnancy maintenance. On the other hand, cytotrophoblasts in the chorionic villi that are anchored to uterine decidua proliferate into cell columns from which some cytotrophoblasts migrate and invade deeper layers of decidua. The migratory and invasive cytotrophoblasts, termed interstitial extravillous trophoblasts (EVTs), may further invade the uterine myometrium and replace the endothelial cells of spiral arteries. This phenomenon, called spiral artery remodeling, is essential for sufficient blood flow into intervillous spaces of the placenta, as remodeled arteries become dilated and nonvasoactive. Indeed, insufficient spiral artery remodeling due to shallow trophoblast invasion may result in placental hypoxia and pregnancy complications such as preeclampsia and intrauterine growth retardation with clinical features of gestational hypertension, proteinuria, and failure of optimal fetal growth (6).Glial cells missing 1 (GCM1), also known as GCMa, is a transcription factor critical for placental developmen...

show abstract

“…118 Furthermore, it appears that LIF transmits an up-regulation of STAT3 expression, activation and DNA-binding activity, which results ultimately in a protease profile alteration that dose-dependently boosts trophoblastic (human choriocarcinoma) invasion and proliferation. 119 Here, cDNA macroarrays found that the expression of TIMP-1 was down-regulated, with TIMP-1 being a protein that binds and thus inactivates MMP-9, or MMP-9, a protein critical for cytotrophoblast invasion. 120,121 Knocking down STAT3 expression in Jeg-3 choriocarcinoma cells, first trimester and term placentae trophoblast through short interfering RNA (siRNA) resulted in a dramatic reduction in invasive potential regardless of LIF supplementation.…”

Section: -105mentioning

confidence: 97%

REVIEW ARTICLE: Governing the Invasive Trophoblast: Current Aspects on Intra‐ and Extracellular Regulation

Fitzgerald

Germeyer

Huppertz

et al. 2010

American J Rep Immunol

Self Cite

View full text Add to dashboard Cite

Citation Fitzgerald JS, Germeyer A, Huppertz B, Jeschke U, Knöfler M, Moser G, Scholz C, Sonderegger S, Toth B, Markert UR. Governing the invasive trophoblast: current aspects on intra‐ and extracellular regulation. Am J Reprod Immunol 2010This review summarizes several aspects especially of regulating factors governing trophoblast invasion. Those include the composition of the extracellular matrix containing a variety of matrix metalloproeinases and their inhibitors, but also intracellular signals. Furthermore, a newly described trophoblast subtype, the endoglandular trophoblast, is presented. Its presence may provide a possible mechanism for opening and connecting uterine glands into the intervillous space. Amongst others, two intracellular signalling pathways are crucial for regulation of trophoblast functions and development: Wnt‐ and signal transducer and activator of transcription (STAT)3 signalling. Wnt signalling promotes implantation, placentation and trophoblast differentiation. Several Wnt‐dependent cascades and regulatory mechanisms display different functions in trophoblast cells. The STAT3 signalling system is fundamental for induction and regulation of invasiveness in physiological trophoblastic cells, but also in tumours. The role of galectins (Gal) in trophoblast regulation and placenta development comes increasingly into focus. The Gal‐ 1–4, 7–10 and 12–14 have been detected in humans. Detailed information is only available for Gal‐1, ‐2, ‐3, ‐4, ‐9 and ‐12 in endometrium and decidua. Gal‐1, ‐3 and ‐13 (‐14) have been detected and studied in trophoblast cells.

show abstract

Leukemia inhibitory factor triggers activation of signal transducer and activator of transcription 3, proliferation, invasiveness, and altered protease expression in choriocarcinoma cells

Cited by 93 publications

References 57 publications

Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression

Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression

High-Temperature Requirement Protein A4 (HtrA4) Suppresses the Fusogenic Activity of Syncytin-1 and Promotes Trophoblast Invasion

REVIEW ARTICLE: Governing the Invasive Trophoblast: Current Aspects on Intra‐ and Extracellular Regulation

Contact Info

Product

Resources

About