Reciprocal expression of epidermal growth factor receptor (EGF-R) and c-erbB2 by non-invasive and invasive human trophoblast populations

Jokhi, Percy; King, Ashley; Loke, Y.W.

doi:10.1016/1043-4666(94)90068-x

Cited by 80 publications

(45 citation statements)

References 22 publications

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“…The expression of EGFR2 (also known as CD340 or ERBB2), LIFR, and, at low level, EGFR1 on EVT is confirmed, and, moreover, a marked increase in expression of EGFR2 and LIFR, but not EGFR1 was observed after culture on fibronectin ( Fig. 1E) (2). VT expressed higher levels of EGFR1 and did not express EGFR2 or LIFR.…”

Section: Resultsmentioning

confidence: 54%

“…The factors required to promote differentiation and proliferation of EVT are unknown but may include interaction with extracellular matrix proteins and growth factors such as epidermal growth factor (EGF), leukemia inhibitory factor (LIF), bone morphogenetic factor-4 (BMP4), and fibroblast growth factor-4 (FGF4) (2)(3)(4)(5). EVT invade decidual tissue and interact with maternal decidual natural killer cells (dNK), decidual macrophages (dMϕ), and decidual T cells (dT) (1,6).…”

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confidence: 99%

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Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Tilburgs

Crespo

Zwan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

165

183

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Invading human leukocyte antigen-G+ (HLA-G+) extravillous trophoblasts (EVT) are rare cells that are believed to play a key role in the prevention of a maternal immune attack on foreign fetal tissues. Here highly purified HLA-G+ EVT and HLA-G− villous trophoblasts (VT) were isolated. Culture on fibronectin that EVT encounter on invading the uterus increased HLA-G, EGF-Receptor-2, and LIFReceptor expression on EVT, presumably representing a further differentiation state. Microarray and functional gene set enrichment analysis revealed a striking immune-activating potential for EVT that was absent in VT. Cocultures of HLA-G+ EVT with sample matched decidual natural killer cells (dNK), macrophages, and CD4+ and CD8+ T cells were established. Interaction of EVT with CD4+ T cells resulted in increased numbers of CD4+CD25 HI FOXP3+CD45RA+ resting regulatory T cells (Treg) and increased the expression level of the Treg-specific transcription factor FOXP3 in these cells. However, EVT did not enhance cytokine secretion in dNK, whereas stimulation of dNK with mitogens or classical natural killer targets confirmed the distinct cytokine secretion profiles of dNK and peripheral blood NK cells (pNK). EVT are specialized cells involved in maternal-fetal tolerance, the properties of which are not imitated by HLA-G-expressing surrogate cell lines.Treg | FOXP3 | NK cell | human | pregnancy

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Section: Resultsmentioning

confidence: 54%

mentioning

confidence: 99%

Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Tilburgs

Crespo

Zwan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

165

183

View full text Add to dashboard Cite

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“…40 During EVT formation, cells downregulate EGFR1 and induce ERBB2 (also termed HER-2/neu) in a similar manner to tumor cells. 41,42 Other studies also demonstrate EGF/EGFR1-induced motility in villous explant cultures and primary cytotrophoblasts. 38,43 Collectively, these studies provide evidence of EGF and it receptors as important regulators of trophoblast cells.…”

Section: Inducers Of Emtmentioning

confidence: 99%

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Davies

Pollheimer

Yong

et al. 2016

Cell Adhesion & Migration

209

146

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A successful pregnancy depends on the intricate and timely interactions of maternal and fetal cells. Placental extravillous cytotrophoblast invasion involves a cellular transition from an epithelial to mesenchymal phenotype. Villous cytotrophoblasts undergo a partial epithelial to mesenchymal transition (EMT) when differentiating into extravillous cytotrophoblasts and gain the capacity to migrate and invade. This review summarizes our current knowledge regarding known regulators of EMT in the human placenta, including the inducers of EMT, upstream transcription factors that control EMT and the downstream effectors, cell adhesion molecules and their differential expression and functions in pregnancy pathologies, preeclampsia (PE) and fetal growth restriction (FGR). The review also describes the research strategies that were used for the identification of the functional role of EMT targets in vitro. A better understanding of molecular pathways driven by placental EMT and further elucidation of signaling pathways underlying the developmental programs may offer novel strategies of targeted therapy for improving feto-placental growth in placental pathologies including PE and FGR.

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“…Especially, the ability of ErbB-4 to mediate signal transduction through EGF family ligands can be profoundly altered by the concomitant expression of ErbB-2 (38). ErbB-2 protein is strongly expressed in EVTs but not villous trophoblasts over the course of pregnancy, whereas ErbB-1 protein expression is not detected in EVTs (28). These findings suggest the possibility that BTC expressed and erbB-4 mRNA levels in human placenta was performed as described in Materials and methods.The amount of mRNA of erbB-1 and erbB-4 was expressed relative to the abundance of b-actin mRNA.…”

Section: Discussionmentioning

confidence: 61%

“…A goat polyclonal antibody against human BTC (R&D System Inc.) and mouse monoclonal antibodies against ErbB-1 (Neo Markers Inc., Fremont, CA, USA) and ErbB-4 (Neo Markers Inc.) were used as primary antibodies. EVTs in term placentas were identified by immunostaining with monoclonal antibodies against ErbB-2 (Neo Markers Inc.) and cytokeratin 7 (Novocastra Laboratories Ltd, Newcastle upon Tyne, UK), which are reliable markers for the identification of EVTs (28,29). To improve the staining efficacy of ErBb-2 and cytokeratin 7, we used the antigen retrieval method (30).…”

Section: Immunohistochemical Stainingmentioning

confidence: 99%

Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy

Tanimura

Nakago²,

Murakoshi³

et al. 2004

European Journal of Endocrinology

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Objective: Betacellulin (BTC), purified and cloned from mouse beta cell tumor (BTC-JC10), is regarded as a new member of the epidermal growth factor family. The present study was conducted to clarify the expression of BTC and its receptors, ErbB-1 and ErbB-4, in the trophoblasts in the human placenta over the course of pregnancy. Design and Methods: Human placental tissues were obtained from 4 pregnant women at the 4th to 5th week of pregnancy (very early placentas), 10 women at the 6th to 12th week (early placentas), 5 women at the 18th to 21st week (mid placentas) and 8 women at the 38th and 40th week (term placentas). The mRNA expressions of BTC, erbB-1 and erbB-4 were evaluated by quantitative RT-PCR with Southern blotting and the expression of the soluble form of BTC was determined by western immunoblot with a specific antibody to BTC protein. Immunohistochemical staining of BTC, ErbB-1 and ErbB-4 was also performed. Results: The levels of BTC mRNA expression in early and mid placentas were significantly higher than those in term placentas. The soluble form of BTC protein with an estimated molecular mass of 9.5 kDa was expressed in early and mid placentas, whereas the soluble form was not detected in term placentas. BTC from very early placentas until mid placentas was immunolocalized in syncytiotrophoblasts (S-cells), and was most abundant in early placentas. In contrast, BTC was immunolocalized in extravillous trophoblasts (EVTs), but not in villous trophoblasts in term placentas. The levels of erbB-1 mRNA in the early and mid placentas were significantly higher than those in term placentas, whereas the levels of erbB-4 mRNA in early placentas were significantly lower than those in mid and term placentas. ErbB-1 was immunolocalized in cytotrophoblasts in very early placentas, whereas it was immunolocalized in S-cells from early until term placentas. ErbB-4 from very early placentas until mid placentas was immunolocalized in S-cells, whereas ErbB-4 in the term placentas was detected in EVTs, but not in villous trophoblasts. Conclusions: These findings provide evidence for changes in expression and cytological localization of BTC and its receptors in the trophoblasts in human placenta over the course of pregnancy. BTC may play a pivotal role as a local growth factor in promoting the differentiated villous trophoblastic function via ErbB-1 in early placentas and in contributing to placental growth through the maintenance of EVT cell function via ErbB-4 in term placentas.

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Reciprocal expression of epidermal growth factor receptor (EGF-R) and c-erbB2 by non-invasive and invasive human trophoblast populations

Cited by 80 publications

References 22 publications

Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Epithelial-mesenchymal transition during extravillous trophoblast differentiation

Changes in the expression and cytological localization of betacellulin and its receptors (ErbB-1 and ErbB-4) in the trophoblasts in human placenta over the course of pregnancy

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