References of "Pequeux, Christel"
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See detailEstrogens and tumor microenvironment
Pequeux, Christel ULg

Conference (2013)

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See detailDifferential expression of Vegfr-2 and its soluble form in preeclampsia.
Munaut, Carine ULg; LORQUET, Sophie ULg; Pequeux, Christel ULg et al

in PLoS ONE (2012), 7(3), 33475

Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably ... [more ▼]

Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta. METHODOLOGY/PRINCIPAL FINDINGS: By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction. [less ▲]

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See detailMT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis
Maquoi, Erik ULg; Assent, Delphine; Detilleux, Julien et al

in Oncogene (2012), 31(4), 480-93

As invading breast carcinoma cells breach their underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic ... [more ▼]

As invading breast carcinoma cells breach their underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumor cells must acquire the capacity to negotiate this novel microenvironment. Collagen influences the fate of epithelial cells by inducing apoptosis. However, the mechanisms used by invading tumor cells to evade collagen-induced apoptosis remain to be defined. We demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP/MMP-14) confers breast cancer cells with the ability to escape apoptosis when embedded in a collagen gel and after orthotopic implantation in vivo. In the absence of MMP-14-dependent proteolysis, type I collagen triggers apoptosis by inducing the expression of the pro-apoptotic Bcl-2-interacting killer in luminal-like breast cancer cells. These findings reveal a new mechanism whereby MMP-14 activity promotes tumor progression by circumventing apoptosis. [less ▲]

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See detailStromal Estrogen Receptor-α Promotes Tumor Growth by Normalizing an Increased Angiogenesis.
Pequeux, Christel ULg; Raymond-Letron, I; Blacher, Silvia ULg et al

in Cancer Research (2012), 72(12), 3010-3019

Estrogens directly promote the growth of breast cancers that express the Estrogen Receptor 􏰀 (ERalpha). However, the contribution of stromal expression of ERalpha in the tumor microenvironment to the pro ... [more ▼]

Estrogens directly promote the growth of breast cancers that express the Estrogen Receptor 􏰀 (ERalpha). However, the contribution of stromal expression of ERalpha in the tumor microenvironment to the pro-tumoral effects of estrogen has never been explored. In this study, we evaluated the molecular and cellular mechanisms by which 17beta-estradiol (E2) impacts the microenvironment and modulates tumor development of ERalpha-negative tumors. Using different mouse models of ER-negative cancer cells grafted subcutaneously into syngeneic ovariectomized immunocompetent mice, we found that E2 potentiates tumor growth, increases intratumoral vessel density and modifies tumor vasculature into a more regularly organized structure, thereby improving vessel stabilization to prevent tumor hypoxia and necrosis. These E2-induced effects were completely abrogated in ERalpha-deficient mice, demonstrating a critical role of host ERα. Notably, E2 did not accelerate tumor growth when ERalpha was deficient in Tie2- positive cells, but still expressed by bone marrow derived cells. These results were extended by clinical evidence of ERalpha-positive stromal cell labeling in the microenvironment of human breast cancers. Together, our findings therefore suggest that E2 promotes the growth of ERalpha-negative cancer cells through the activation of stromal ERα (not hematopoiteic but Tie2-dependent expression of ERalpha), which normalizes tumor angiogenesis and allows an adaptation of blood supply to tumor demand preventing hypoxia and necrosis. These findings significantly deepen mechanistic insights into the impact of E2 on tumor development with potential consequences for cancer treatment. [less ▲]

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See detailTGFbeta-receptor-dependent angiostimulation through the hyperglycosylated isoform of human chorionic gonadotropin.
Berndt, Sarah; Detilleux, Julien; Blacher, Silvia et al

in Placenta (2011), 32(9), 44

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See detailAetiology and physiopathology of preeclampsia and related forms.
Lorquet, Sophie ULg; Pequeux, Christel ULg; Munaut, Carine ULg et al

in Acta Clinica Belgica (2010), 65(4), 237-41

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and oedema, resolves on placental delivery. Its pathogenesis is thought to be associated to a hypoxic placenta ... [more ▼]

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and oedema, resolves on placental delivery. Its pathogenesis is thought to be associated to a hypoxic placenta. Placental hypoxia is responsible for the maternal vascular dysfunction via the increased placental release of anti-angiogenic factors such as soluble flt1 and endoglin. These soluble receptors bind VEGF, PLGF and TGFbeta1 and 3 in the maternal circulation, causing endothelial dysfunction in many maternal tissues. Despite these recent and important new molecular findings, it is important to consider that normal pregnancy is also characterized by systemic inflammation, oxidative stress and alterations in levels of angiogenic factors and vascular reactivity. Both the placenta and maternal vasculatures are major sources of reactive oxygen and nitrogen species which can produce powerful pro-oxidants that covalently modify proteins and alter vascular function in preeclampsia. Finally, the recent demonstration of activating auto-antibodies to the Angiotensin 1 receptor that experimentally play a major pathogenic role in preeclampsia further indicates the pleiotropism of aetiologies of this condition. [less ▲]

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See detailSoluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment.
LORQUET, Sophie ULg; Berndt, Sarah; Blacher, Silvia ULg et al

in FASEB Journal (2010), 24(10), 3782-95

Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF ... [more ▼]

Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF agents. Here, we report that these soluble receptors contribute to vessel maturation by mediating a dialogue between endothelial cells (EC) and mural cells that leads to blood vessel stabilization. Through a multidisciplinary approach, we provide evidences that these soluble VEGF receptors promote mural cell migration through a paracrine mechanism involving interplay in EC between VEGF/VEGFR-2 and sphingosine-1- phosphate type-1 (S1P)/S1P1 pathways that leads to endothelial nitric oxyde synthase (eNOS) activation. This new paradigm is supported by the finding that sVEGFR-1 and -2: 1) induce an eNOS-dependent outgrowth of a mural cell network in an ex vivo model of angiogenesis, 2) increase the mural cell coverage of neovessels in vitro and in vivo, 3) promote mural cell migration towards EC, 4) stimulate endothelial S1P1 overproduction and eNOS activation that promote the migration and the recruitment of neighboring mural cells. These findings provide new insights into mechanisms regulating physiological and pathological angiogenesis and vessel stabilization. [less ▲]

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See detailChorionic Gonadotropin Stimulation of Angiogenesis and Pericyte Recruitment
Berndt, Sarah; Blacher, Silvia ULg; PERRIER d'HAUTERIVE, Sophie ULg et al

in Journal of Clinical Endocrinology and Metabolism (2009), 94(11), 4567-74

During the periimplantation period, human chorionic gonadotropin (hCG) plays a key role by increasing the uterine blood flow through uterine vessel vasodilatation but also through angiogenesis. Indeed, we ... [more ▼]

During the periimplantation period, human chorionic gonadotropin (hCG) plays a key role by increasing the uterine blood flow through uterine vessel vasodilatation but also through angiogenesis. Indeed, we previously demonstrated that hCG contributes to endothelial cell recruitment and vessel formation. OBJECTIVE: In this study, hCG was proposed as an arteriogenic factor that could promote perivascular cell recruitment and vessel stabilization. DESIGN: The aortic ring assay, a three-dimensional ex vivo angiogenesis system mimicking all the steps of the angiogenesis process was used to study the impact of hCG on pericyte recruitment and vessel maturation. SETTING: The study was conducted at a university hospital laboratory. MAIN OUTCOME MEASURES: Perivascular cell proliferation, migration, and apposition were quantified by computerized image analysis. RESULTS: Physiological concentrations of hCG (10-400 IU/ml) significantly enhanced pericyte sprouting and migration and gave rise to the maturation and coverage of endothelial capillaries. In a three-dimensional coculture model of endothelial and perivascular cells, hCG enhanced vessel tube formation and endothelial/mural cell adhesion. In addition, hCG stimulated the proliferation of human umbilical vein endothelial cells and smooth muscle cells. The specificity of these effects was determined by using an anti-hCG blocking antibody. Signaling pathways implicated on this hCG effect is protein kinase A and phospholipase C/protein kinase C dependent for the proliferative effect but only phospholipase C/protein kinase C for the migrative process. CONCLUSIONS: Our findings highlight a novel paracrine role of this early embryonic signal in vessel maturation by stimulating perivascular cell recruitment, migration, and proliferation. [less ▲]

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See detailLes défauts d'implantation placentaire et leurs conséquences sur la fonction endothéliale maternelle
Foidart, Jean-Michel ULg; Noël, Agnès ULg; Chantraine, Frédéric ULg et al

in Bulletin Académique National de Médecine (2009), 193(5), 1059-66

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See detailHypoxia is responsible for soluble vascular endothelial growth factor receptor-1 (VEGFR-1) but not for soluble endoglin induction in villous trophoblast
Munaut, Carine ULg; Lorquet, Sophie ULg; Pequeux, Christel ULg et al

in Human Reproduction (2008), 23(6), 1407-15

BACKGROUND: Pre-eclampsia is a pregnancy disorder characterized by a maternal endothelial cell dysfunction associated with low levels of circulating placental growth factor (PlGF) and increased levels of ... [more ▼]

BACKGROUND: Pre-eclampsia is a pregnancy disorder characterized by a maternal endothelial cell dysfunction associated with low levels of circulating placental growth factor (PlGF) and increased levels of total vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1), and soluble endoglin, a transforming growth factor b1 and 3 coreceptor. Here, we tested the hypothesis that these altered levels of angiogenic cytokines and of the anti-angiogenic soluble forms of cytokine receptors could be the consequence of hypoxia. METHODS: Normal human umbilical vein endothelial cells, immortalized first trimester extravillous trophoblast cells (HTR8/SVneo) and first trimester placental villi explants (8–14 weeks) were used for culture under normoxia (20% O2) or hypoxia (1% O2). Culture media were collected for the measurement of cytokines by enzyme-linked immunosorbent assay. Total RNA was extracted for RT-PCR analysis. RESULTS: Under hypoxia, villous trophoblast expressed higher levels of VEGF, VEGFR-1, sVEGFR-1 and VEGFR-2 mRNAs (P < 0.001), and secreted more VEGF and sVEGFR-1 proteins (P < 0.05). In contrast, PlGF mRNA and protein were decreased in 1% O2 (P < 0.001), whereas endoglin (Eng) was not modulated. Additionally, sVEGFR-1 directly abolished VEGF/PlGF-induced angiogenesis in the rat aortic ring assay. CONCLUSIONS: Our results support the hypotheses that, in pre-eclampsia, (i) overproduction of VEGF family factors by pre-eclamptic placenta is a consequence of induced hypoxia; (ii) overproduction of sVEGFR-1 by hypoxic villous trophoblast accounts for maternal free VEGF depletion; (iii) low circulating level of free PlGF is not only related to sVEGFR-1 overproduction, but also to hypoxia induced mRNA down-regulation; (iv) Eng is not modulated by hypoxia.. [less ▲]

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See detailImplication of soluble receptors of VEGF, sVEGFR-1 and sVEGFR-2, in angiogenesis
Lorquet, Sophie ULg; Berndt, Sarah ULg; Blacher, Silvia ULg et al

in American Journal of Reproductive Immunology (2008), 60/1

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See detailImplication of VEGF receptor soluble forms, sVEGFR-1 and sVEGFR-2, in angiogenesis
Lorquet, Sophie ULg; Berndt, Sarah ULg; Blacher, Silvia ULg et al

in Acta Clinica Belgica (2008), 63/1

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See detailPlasma oxytocin levels and anxiety in patients with major depression
Scantamburlo, Gabrielle ULg; Hansenne, Michel ULg; Fuchs, Sonia et al

in Psychoneuroendocrinology (2007), 32(4), 407-410

Cerebrospinal fluid and plasmatic levels of oxytocin (OT) have been found to change in mood disorders. In post-mortem studies, the numbers of OT-expressing neurons in the paraventricular nucleus have been ... [more ▼]

Cerebrospinal fluid and plasmatic levels of oxytocin (OT) have been found to change in mood disorders. In post-mortem studies, the numbers of OT-expressing neurons in the paraventricular nucleus have been reported to be increased. Moreover, OT is considered as an endogenous antistress hormone. It has also revealed antidepressive effects. OT may contribute to the dysregulation of the HPA system in major depression. The aim of the study was to assess a possible relationship between anxiety and plasma oxytocin (OT) Levels in depressive patients. Severity of depression was estimated with the Hamilton Depression Rating Scale and anxiety by using the Spielberger State-Anxiety Inventory. Results showed a significant negative correlation between oxytocin and the scored symptoms depression (r = -0.58, p = 0.003) and anxiety (r = -0.61, p = 0.005). (C) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailAngiogenic activity of human chorionic gonadotropin through LH receptor activation on endothelial and epithelial cells of the endometrium
Berndt, Sarah ULg; PERRIER d'HAUTERIVE, Sophie ULg; Blacher, Silvia ULg et al

in FASEB Journal (2006), 20(14), 2630-2632

Successful embryo development requires an extensive endometrial angiogenesis in proximity of implantation site. The glycoprotein hCG is produced even before implantation by trophoblast in normal pregnancy ... [more ▼]

Successful embryo development requires an extensive endometrial angiogenesis in proximity of implantation site. The glycoprotein hCG is produced even before implantation by trophoblast in normal pregnancy. In this manuscript, we demonstrate an angiogenic effect of hCG in several in vivo (chick chorioallantoic membrane, matrigel plug assay, aortic ring assay) and in vitro experimental models. In contrast, human placental lactogen (hPL) did not display angiogenic properties. LH/hCG receptor was detected in endothelial cells by reverse-transcriptase polymerase chain reaction (RT-PCR) and by Western blotting. In mice aortic ring assay, angiostimulation by hCG was abrogated by deletion of LH/hCG receptor (LuRKO mice). Use of recombinant hCG and anti-hCG antibody (Ab) further confirmed the specificity of this angiogenic activity. By using dibutyryl cAMP, adenylate cyclase, or protein kinase A inhibitors, we demonstrate that hCG-mediated angiogenesis involves adenylyl-cyclase-protein kinase A activation. Addition of hCG to endometrial epithelial epithelial cells, but not to cultured endothelial cells, stimulated vascular endothelial growth factor (VEGF). VEGF and hCG also displayed additive activities. Altogether, these data demonstrate that peritrophoblastic angiostimulation may result from a paracrine dialogue between trophoblast, epithelial, and endothelial cells through hCG and VEGF. [less ▲]

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See detailProvasopressin expression by breast cancer cells: implications for growth and novel treatment strategies
Keegan, B. P.; Akerman, B. L.; Pequeux, Christel ULg et al

in Breast Cancer Research and Treatment (2006), 95(3), 265-277

The arginine vasopressin (AVP) gene is expressed in certain cancers such as breast cancer, where it is believed to act as an autocrine growth factor. However, little is known about the regulation of the ... [more ▼]

The arginine vasopressin (AVP) gene is expressed in certain cancers such as breast cancer, where it is believed to act as an autocrine growth factor. However, little is known about the regulation of the AVP protein precursor (proAVP) or AVP-mediated signaling in breast cancer and this study was undertaken to address some of the basic issues. The cultured cell lines examined (Mcf7, Skbr3, BT474, ZR75, Mcf10a) and human breast cancer tissue extract were found to express proAVP mRNA. Western analysis revealed multiple forms of proAVP protein were present in cell lysates, corresponding to those detected in human hypothalamus extracts. Monoclonal antibodies directed against different regions of proAVP bound to intact live Mcf7 and Skbr3 cells. Dexamethasone increased the amount of proAVP-associated glycopeptide (VAG) secreted by Skbr3 cells and a combination of dexamethasone, IBMX and 8br-cAMP increased cellular levels of VAG. Exogenous AVP (1, 10, and 100 nM) elevated phospho-ERK1/2 levels, and increased cell proliferation was observed in the presence of 10 nM AVP. Concurrent treatment with the V1a receptor antagonist SR49059 reduced the effects of AVP on proliferation in Mcf7 cells, and abolished it in Skbr3 cells. Results here show that proAVP components are found at the surface of Skbr3 and Mcf7 cells and are also secreted from these cells. In addition, they show that AVP promotes cancer cell growth, apparently through a V1-type receptor-mediated pathway and subsequent ERK1/2 activation. Thus, strategies for targeting proAVP should be examined for their effectiveness in diagnosing and treating breast cancer. [less ▲]

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