Molecular mechanisms of type I collagen-induced apoptosis in breast carcinoma cells
Maquoi, Erik ; Assent, Delphine ; Foidart, Jean-Michel et al
Poster (2013, September 27)
Objective: As invading breast carcinoma cells breach the underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop ... [more ▼]
Objective: As invading breast carcinoma cells breach the underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumour cells must acquire the capacity to negotiate this hostile microenvironment. By enmeshing cells in a dense fibrillar network, type I collagen acts as a physical barrier for cell migration as well as an endogenous antigrowth signal, partly by inducing apoptosis in epithelial cells. Aberrant cell survival resulting from an acquired resistance toward apoptosis represents a prominent hallmark of cancers. However, the molecular mechanisms implicated in collagen-induced apoptosis remain poorly defined. Here, we investigate the molecular mechanisms by which type I collagen induces apoptosis in breast carcinoma cells and identify MMP-14, a membrane-anchored matrix metalloproteinase, as a key anti-apoptotic factor. Methods: To investigate the induction of apoptosis by collagen, human breast adenocarcinoma MCF-7 cells overexpressing or not MMP-14 were plated on plastic plates or embedded within three dimensional type I collagen gels (Col3D). Cell death was evaluated by measuring cytoplasmic histone-associated DNA fragments (Cell Death Detection ELISA). The percentage of cells with an apoptotic nuclear morphology was also determined. The interactions between cancer cells and Col3D were analyzed by confocal microscopy and the impact of Col3D on the transcriptome of cancer cells was investigated using Illumina HT-12 BeadArrays. Results: When cultured within Col3D gels, MCF-7 cells displayed a round morphology and a cell death characterized by a Z-VAD-FMK-dependent chromatin condensation, nuclear segmentation and oligonucleosomal DNA fragmentation was induced. Transfection of MCF-7 cells with MMP-14 cDNA promoted the interactions between cells and collagen and prevented apoptosis. A transcriptomic analysis revealed that culturing MCF-7 cells within Col3D altered the expression of about 700 genes, irrespective of MMP-14 expression. Col3D modulated the expression of several apoptosis-related genes. Interestingly, MMP-14 activity was sufficient to prevent the Col3D-dependent induction of Bcl2-Interacting Killer (BIK), a pro-apoptotic member of the Bcl-2 family. Conclusions: Our results shed light on the molecular mechanisms by which a collagen-rich microenvironment triggers apoptosis in invading breast cancer cells. Furthermore, we demonstrate that MMP-14 promotes tumour progression by circumventing apoptosis. [less ▲]Detailed reference viewed: 20 (2 ULg)
Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression.
Koopmansch, Benjamin ; ; Foidart, Jean-Michel et al
in Biochemical and Biophysical Research Communications (2013), 431(4), 652
E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the ... [more ▼]
E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the proximal region of the E-cadherin gene promoter. We have here explored a potential competition between ZEB2 and KLF4 for the binding to the E-cadherin promoter. We show an inverse correlation between ZEB2 expression levels and KLF4 recruitment on the E-cadherin promoter in three breast cancer cell lines and in A431/HA.ZEB2 cells in which ZEB2 expression is induced by doxycycline (DOX). We identified a region of the E-cadherin promoter bound by KLF4 which is necessary for the activation of the E-cadherin promoter activity after KLF4 overexpression. This region is localized between positions -28 and -10 and thus overlaps with one of the ZEB2 binding sites. Deleting the bipartite ZEB2 binding site results in increased KLF4 induced E-cadherin promoter activity. Taken together, our results suggest that E-cadherin expression in cancer cells is controlled by a balance between ZEB2 and KLF4 expression levels. [less ▲]Detailed reference viewed: 60 (26 ULg)
Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice.
LAMBERT, Vincent ; Lecomte, Julie ; Hansen, Sylvain et al
in Nature Protocols (2013), 8(11), 2197-2211
The mouse model of laser-induced choroidal neovascularization (CNV) has been used extensively in studies of the exudative form of age-related macular degeneration (AMD). This experimental in vivo model ... [more ▼]
The mouse model of laser-induced choroidal neovascularization (CNV) has been used extensively in studies of the exudative form of age-related macular degeneration (AMD). This experimental in vivo model relies on laser injury to perforate Bruch's membrane, resulting in subretinal blood vessel recruitment from the choroid. By recapitulating the main features of the exudative form of human AMD, this assay has served as the backbone for testing antiangiogenic therapies. This standardized protocol can be applied to transgenic mice and can include treatments with drugs, recombinant proteins, antibodies, adenoviruses and pre-microRNAs to aid in the search for new molecular regulators and the identification of novel targets for innovative treatments. This robust assay requires 7-14 d to complete, depending on the treatment applied and whether immunostaining is performed. This protocol includes details of how to induce CNV, including laser induction, lesion excision, processing and different approaches to quantify neoformed vasculature. [less ▲]Detailed reference viewed: 8 (2 ULg)
Evidence for cross-talk between the LH receptor and LH during implantation in mice
Gridelet, Virginie ; ; et al
in Reproduction, Fertility and Development (2013), 25
The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model ... [more ▼]
The present study investigated the first interaction that occurs between the blastocyst and endometrium during implantation. Given the ethical objections to studying implantation in humans, a mouse model was used to study the dialogue between luteinising hormone (LH) and luteinising hormone receptor (LHCGR). Several studies performed on LHCGR-knockout mice have generated controversy regarding the importance of the dialogue between LH and LHCGR during implantation. There has been no demonstration of a bioactive LH-like signal produced by the murine blastocyst. The first aim of the present study was to examine and quantify, using radioimmunoassay, the generation of a bioactive LH signal by the murine blastocyst. We went on to examine and quantify endometrial Lhcgr expression to validate the mouse model. Expression of LHCGR in mouse uteri was demonstrated using immunohistochemistry and western blot analysis. To quantify the expression of Lh in the mouse blastocyst and Lhcgr in the endometrium, reverse transcription–polymerase chain reaction (RT-PCR) and real-time quantitative (q) RT-PCR were performed. The results demonstrate that Lhcgr expression in BALB/c mouse endometrial epithelium is increased at the time of implantation and indicate that LHCGR may contribute to the implantation process. In support of this hypothesis, we identified a bioactive LH signal at the time of murine blastocyst implantation. [less ▲]Detailed reference viewed: 13 (3 ULg)
Expression of the gamma 2 chain of laminin-332 in eutopic and ectopic endometrium of patients with endometriosis.
; Nisolle, Michelle ; et al
in Reproductive biology and endocrinology (2013), 11(1), 94
BACKGROUND: Endometrial cells, which are shed by retrograde menstruation, may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to ... [more ▼]
BACKGROUND: Endometrial cells, which are shed by retrograde menstruation, may aberrantly express molecules involved in invasion and migration, leading to endometriosis. The aim of this study was to investigate the expression of the laminin gamma 2 chain (LAMC2) in the tissues of women with and without endometriosis. METHODS: Endometrial biopsy specimens were collected from healthy volunteers and from endometriosis patients. Biopsy specimens from the corresponding endometriotic lesions were also collected. The expression of laminin gamma 2 chain was evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Endometrial tissue from women with or without endometriosis showed constitutive expression of LAMC2 mRNA throughout the menstrual cycle. A higher mRNA level was observed in ectopic endometrium (Ec) from women with endometriosis compared with eutopic endometrium (Eu) from women with endometriosis. Immunohistochemistry revealed a varied pattern of laminin gamma 2 chain expression, with increased epithelial expression in eutopic endometrium from women with endometriosis compared with those without endometriosis. CONCLUSIONS: The altered expression of laminin gamma 2 chain in eutopic endometrium from women with endometriosis may provide new opportunities for diagnosis and treatment. [less ▲]Detailed reference viewed: 10 (3 ULg)
Sunitinib inhibits inflammatory corneal lymphangiogenesis.
Detry, Benoît ; Blacher, Silvia ; Erpicum, Charlotte et al
in Investigative Ophthalmology & Visual Science (2013), 54(5), 3082-93
PURPOSE: To evaluate the antilymphangiogenic potential of multi-target tyrosine kinase inhibitor sunitinib in corneal neovascularization (NV). METHODS: Inflammatory corneal NV was induced by thermal ... [more ▼]
PURPOSE: To evaluate the antilymphangiogenic potential of multi-target tyrosine kinase inhibitor sunitinib in corneal neovascularization (NV). METHODS: Inflammatory corneal NV was induced by thermal cauterization applied in the central cornea of mice, to which sunitinib malate was daily administered by gavage or not. At days 6, 11, or 17 post cauterization, lymphatic and blood vessels, as well as inflammatory cells were immunostained and quantified in whole-mounted corneas. RT-PCRs were performed to evidence VEGF-A, VEGF-C, VEGF-D, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor (VEGFR)-1 and -2 (sVEGFR-1, sVEGFR-2) expressions. Macrophages were isolated from mice peritoneal cavity following thioglycollate injection to produce conditioned medium. The effects of sunitinib were evaluated in vitro in the aortic and lymphatic ring assays in the presence or not of macrophage conditioned medium. RESULTS: Sunitinib treatment drastically reduced pathologic corneal lymphangiogenesis and angiogenesis. Reduced F4/80+ cell infiltration was evidenced in sunitinib-treated mice and was associated to decreased VEGF-A (by 50%, P < 0.01) and VEGF-C (by 35%, P < 0.01) expressions, while VEGF-D and sVEGFR-2 expressions were not affected. In vitro, sunitinib dose-dependently inhibited aortic ring outgrowth, but failed to affect lymphangiogenesis in the lymphatic ring assay. However, macrophage conditioned medium-enhanced angiogenesis and lymphangiogenesis were both strongly counteracted by sunitinib treatment. Mechanistically, sunitinib blocked VEGFR-2 phosphorylation induced by VEGF-A released by macrophages. CONCLUSIONS: Sunitinib exerts antihemangiogenic and antilymphangiogenic effects in vivo by reducing F4/80+ cell recruitment and interacting with their released factors. [less ▲]Detailed reference viewed: 11 (3 ULg)
Histology of the vaginal wall in women with pelvic organ prolapse: a literature review.
DE LANDSHEERE, Laurent ; Munaut, Carine ; Richelle, Betty et al
in International Urogynecology Journal (2013), sous presse
INTRODUCTION AND HYPOTHESIS: The pathophysiology of pelvic organ prolapse (POP) is incompletely understood. The purpose of this study is to describe the current knowledge about histology of the vaginal ... [more ▼]
INTRODUCTION AND HYPOTHESIS: The pathophysiology of pelvic organ prolapse (POP) is incompletely understood. The purpose of this study is to describe the current knowledge about histology of the vaginal wall and its possible involvement in the pathogenesis of pelvic organ prolapse. METHODS: Eligible studies were selected through a MEDLINE search covering January 1986 to December 2012. The research was limited to English-language publications. RESULTS: Investigations of changes in the vaginal tissue that occur in women with genital prolapse are currently still limited and produced contrary results. The heterogeneity of the patients and the control groups in terms of age, parity and hormonal status, of the localization of biopsies and the histological methods as well as the lack of validation of the quantification procedures do not allow clear and definitive conclusions to be drawn. CONCLUSIONS: This review shows that current knowledge of the histological changes observed in women with POP are inconclusive and relatively limited. More studies are needed in this specific field to better understand the mechanisms that lead to POP. [less ▲]Detailed reference viewed: 23 (3 ULg)
Hyperglycosylated human chorionic gonadotropin stimulates angiogenesis through TGF-beta receptor activation.
; Blacher, Silvia ; Munaut, Carine et al
in FASEB Journal (2013), 27(4), 1309-21
Embryo implantation requires extensive angiogenesis at the maternal-fetal interface. Hyperglycosylated human chorionic gonadotropin (hCG-H), a trophoblast invasive signal produced by extravillous ... [more ▼]
Embryo implantation requires extensive angiogenesis at the maternal-fetal interface. Hyperglycosylated human chorionic gonadotropin (hCG-H), a trophoblast invasive signal produced by extravillous cytotrophoblasts and by choriocarcinoma, was evaluated for its angiogenic role. hCG-H was purified by HPLC from choriocarcinoma supernatant, and the glycosylation pattern was determined by 2D gel analysis. Angiogenesis models used were aortic ring assay with wild-type and LHCGR-knockout mice, endothelial and mural cell proliferation, and migration assays. The TGF-beta signaling pathway was studied by coimmunoprecipitation, competitive binding, TGF-beta reporter gene assays, and Smad immunoblotting. hCG-H displayed a potent angiogenic effect [3.2-fold increase of number of vessel intersections in wild-type aortic rings (11.406 to 36.964)]. hCG-H-induced angiostimulation was independent of the classic hCG signaling pathway since it persisted in LHCGR-knockout mice [4.73-fold increase of number of vessel intersections (10.826 to 51.288)]. Using TGF-beta signaling inhibitors, Tbeta-RII was identified as the hCG-H receptor responsible for its angiogenic switch. hCG-H exposure enhanced phosphorylation of Smad 2 in endothelial and mural cells and genomic activation of Smad-responsive elements. Interaction between hCG-H and Tbeta-RII was demonstrated by coimmunoprecipitation and binding competition with (125)I-TGF-beta. This new paracrine interaction between trophoblast and endothelial cells through the hCG-H and the TGF-beta receptor complex plays a key role in angiogenesis associated with placental development and tumorigenesis. [less ▲]Detailed reference viewed: 25 (6 ULg)
Impact of follicular G-CSF quantification on subsequent embryo transfer decisions: a proof of concept study.
; Gridelet, Virginie ; RAVET, Stéphanie et al
in Human Reproduction (2013), 28(2), 406-13
BACKGROUND: Previous experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing ... [more ▼]
BACKGROUND: Previous experiments have shown that granulocyte colony-stimulating factor (G-CSF), quantified in the follicular fluid (FF) of individual oocytes, correlates with the potential for an ongoing pregnancy of the corresponding fertilized oocytes among selected transferred embryos. Here we present a proof of concept study aimed at evaluating the impact of including FF G-CSF quantification in the embryo transfer decisions. METHODS: FF G-CSF was quantified with the Luminex XMap technology in 523 individual FF samples corresponding to 116 fresh transferred embryos, 275 frozen embryos and 131 destroyed embryos from 78 patients undergoing ICSI. RESULTS: Follicular G-CSF was highly predictive of subsequent implantation. The receiving operator characteristics curve methodology showed its higher discriminatory power to predict ongoing pregnancy in multivariate logistic regression analysis for FF G-CSF compared with embryo morphology [0.77 (0.69-0.83), P < 0.001 versus 0.66 (0.58-0.73), P = 0.01)]. Embryos were classified by their FF G-CSF concentration: Class I over 30 pg/ml (a highest positive predictive value for implantation), Class II from 30 to 18.4 pg/ml and Class III <18.4 pg/ml (a highest negative predictive value). Embryos derived from Class I follicles had a significantly higher implantation rate (IR) than those from Class II and III follicles (36 versus 16.6 and 6%, P < 0.001). Embryos derived from Class I follicles with an optimal morphology reached an IR of 54%. Frozen-thawed embryos transfer derived from Class I follicles had an IR of 37% significantly higher than those from Class II and III follicles, respectively, of 8 and 5% (P < 0.001). Thirty-five per cent of the frozen embryos but also 10% of the destroyed embryos were derived from G-CSF Class I follicles. Non-optimal embryos appear to have been transferred in 28% (22/78) of the women, and their pregnancy rate was significantly lower than that of women who received at least one optimal embryo (18 versus 36%, P = 0.04). CONCLUSIONS: Monitoring FF G-CSF for the selection of embryos with a better potential for pregnancy might improve the effectiveness of IVF by reducing the time and cost required for obtaining a pregnancy. [less ▲]Detailed reference viewed: 15 (3 ULg)
Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation
Labied, Soraya ; Delforge, Yves ; Munaut, Carine et al
in Transplantation (2013), 95(3), 426-433
Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ... [more ▼]
Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ovarian graft causes massive follicle loss by apoptosis. VEGF111 is a recently described VEGF isoform that does not bind to the extracellular matrix, diffuse extensively and is resistant to proteolysis. These properties confer a significantly higher angiogenic potential to VEGF111 in comparison to the other VEGF isoforms. Methods: We evaluated the morphology of cryopreserved sheep ovarian cortex, grafted in the presence or absence of VEGF111. Ovarian cortex biopsies were embedded in type I collagen with or without VEGF111 addition before transplantation to SCID mice ovaries. Transplants were retrieved 3 days or 3 weeks later. Follicular density, vasculature network, haemoglobin content and cell proliferation were analysed. Results: Addition of VEGF111 increased density of functional capillaries (p=0.01) 3 days after grafting. By double immunostaining of Ki-67 and von Willebrand Factor (vWF) we demonstrated that proliferating endothelial cells were found in 83% of the VEGF111 group when compared to 33% in the control group (p=0.001). This angio-stimulation was associated with a significant enhancement of haemoglobin content (p=0.03). Three weeks after transplantation, the number of primary follicles was significantly higher in VEGF111 grafts (p=0.02). Conclusion: VEGF111 accelerates blood vessels recruitment, functional angiogenesis and improves the viability of ovarian cortex by limiting ischemia and ovarian cortex damage. [less ▲]Detailed reference viewed: 29 (10 ULg)
Use of Sheep Ovarian Tissue as a Model to Restore Fertility in Young Cancerous Women
Fransolet, Maïté ; HENRY, Laurie ; Rozet, Eric et al
Poster (2012, December 10)Detailed reference viewed: 39 (9 ULg)
Expression et localisation spatio-temporelle de KISS1 et de son récepteur KISSR dans le placenta normal et pathologique.
VALDES SOCIN, Hernan Gonzalo ; Munaut, Carine ; CHAVEZ, Viviana et al
Poster (2012, October)
Objectif : Etudier l’expression de KISS1 (métastatine) et de son récepteur KISS1R lors de la grossesse normale et pathologique. Matériels et méthodes : Nous avons étudié la localisation de KISS1 et KISS1R ... [more ▼]
Objectif : Etudier l’expression de KISS1 (métastatine) et de son récepteur KISS1R lors de la grossesse normale et pathologique. Matériels et méthodes : Nous avons étudié la localisation de KISS1 et KISS1R par immunohistochimie dans des placentas normaux (1 er et 3 ème trimestre). Par RT-PCR quantitative, nous avons évalué le niveau d’expression des ARNm dans les placentas et les lits placentaires correspondants. Les niveaux d’expression de ARNm ont été comparés entre les grossesses normales (GN, n=13) et les grossesses spathologiques Prééclampsiques -PE-, n=17 et retard de croissance intrautérine -RCIU-, n=9). Résultats : Au premier trimestre des GN, KISS1 est majoritairement localisé dans les syncitiotrophoblastes, alors que KISS1R est détecté dans le mesenchyme villositaire. Au cours du troisième trimestre, KISS1 est uniquement localisé dans le syncitiotrophoblaste au contact avec la décidue et dans le mésenchyme villositaire et KISS1R est détecté dans le trophoblaste extra-villeux ainsi que dans quelques cellules de la décidue. Les analyses par RT-PCR mettent en évidence une expression plus importante des ARNm de KISS1 (p<0,001) et de KISS1R (p=0.039) dans les placentas (GN,PE et RCIU) par rapport aux lits placentaires correspondants. Les niveaux d’expression de KISS1 et KISS1R ne sont pas, cependant, significativement modulés dans les grossesses pathologiques. Conclusions : Par immunohistochimie, nos résultats indiquent une expression spatiotemporelle différente pour KISS1 et KISS1R entre le 1 er et 3 ème trimestre des grossesses normales. Nous n’avons pas mis en évidence de modulation de l’expression des ARNm dans les grossesses pathologiques. [less ▲]Detailed reference viewed: 26 (4 ULg)
Implant comprising a core and a tube encasing the core
; ; et al
The present invention relates to an implant comprising: - a core material comprising polydimethylsiloxane or at least one hydrogel polymer; - a tube encasing said core material comprising an ethylene ... [more ▼]
The present invention relates to an implant comprising: - a core material comprising polydimethylsiloxane or at least one hydrogel polymer; - a tube encasing said core material comprising an ethylene vinyl acetate polymer or at least one hydrogel polymer; - a sealant for closure of the open ends of said tube comprising polydimethylsiloxane or a mono-, di-, or triacetoxy derivative thereof, or at least one hydrogel polymer; and - at least one active ingredient; with the proviso that when the sealant is said at least one hydrogel polymer, the core material comprises polydimethylsiloxane. Furthermore, the invention relates to an implant for use as a medicament. In particular, the invention relates to an implant for use in the treatment of endometriosis. [less ▲]Detailed reference viewed: 20 (10 ULg)
Matrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collagenase.
Detry, Benoît ; Erpicum, Charlotte ; Paupert, Jenny et al
in Blood (2012), 119(21), 5048-56
Lymphatic dysfunctions are associated with several human diseases, including lymphedema and metastatic spread of cancer. Although it is well recognized that lymphatic capillaries attach directly to ... [more ▼]
Lymphatic dysfunctions are associated with several human diseases, including lymphedema and metastatic spread of cancer. Although it is well recognized that lymphatic capillaries attach directly to interstitial matrix mainly composed of fibrillar type I collagen, the interactions occurring between lymphatics and their surrounding matrix have been overlooked. In this study, we demonstrate how matrix metalloproteinase (MMP)–2 drives lymphatic morphogenesis through Mmp2-gene ablation in mice, mmp2 knockdown in zebrafish and in 3D-culture systems, and through MMP2 inhibition. In all models used in vivo (3 murine models and thoracic duct development in zebrafish) and in vitro (lymphatic ring and spheroid assays), MMP2 blockage or down-regulation leads to reduced lymphangiogenesis or altered vessel branching. Our data show that lymphatic endothelial cell (LEC) migration through collagen fibers is affected by physical matrix constraints (matrix composition, density and cross-linking). Transmission electron microscopy (TEM) and confocal reflection microscopy using DQ-collagen highlight the contribution of MMP2 to mesenchymal-like migration of LEC associated with collagen fiber remodeling. Our findings provide new mechanistic insight into how LEC negotiate an interstitial type I collagen barrier and reveal an unexpected MMP2-driven collagenolytic pathway for lymphatic vessel formation and morphogenesis. [less ▲]Detailed reference viewed: 137 (59 ULg)
The actors of human implantation: gametes, embryo and endometrium
Gridelet, Virginie ; GASPARD, Olivier ; Polese, Barbara et al
in Violin Pereira, Luis Antonio (Ed.) Embryology - Updates and Highlights on Classic Topics (2012)Detailed reference viewed: 17 (5 ULg)
Differential expression of Vegfr-2 and its soluble form in preeclampsia.
Munaut, Carine ; LORQUET, Sophie ; Pequeux, Christel 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 ▲]Detailed reference viewed: 27 (7 ULg)
MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis
Maquoi, Erik ; ; 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 ▲]Detailed reference viewed: 81 (17 ULg)
Individual decisions in placenta increta and percreta: a case series.
CHANTRAINE, Frédéric ; NISOLLE, Michelle ; PETIT, Philippe et al
in Journal of Perinatal Medicine (2012), 40(3), 265-70
Abstract Objective: Placenta increta or percreta is an uncommon pathology, sometimes associated with high maternal morbidity. Its prevalence increases proportionally to the number of cesarean sections ... [more ▼]
Abstract Objective: Placenta increta or percreta is an uncommon pathology, sometimes associated with high maternal morbidity. Its prevalence increases proportionally to the number of cesarean sections. This study analyzed the changes of our management strategy to devise treatment guidelines for this uncommon disorder. Materials and methodology: Between 2005 and 2011, 10 cases of placenta increta or percreta were managed at our university hospital maternity department. Results: Among the 10 cases, seven were diagnosed prenatally. Two patients were diagnosed early, at 14 and 17 weeks of gestational age, and their pregnancies were terminated. Five had hysterectomies during the intrapartum period, and despite attempted conservative treatment for the two others, hysterectomy proved necessary 2 months postpartum because of intrauterine infections. Seven of the 10 women had hysterectomies. Conclusion: Prenatal diagnosis of placenta increta or percreta is essential to plan the delivery in a competent tertiary care center. The decision to perform a cesarean hysterectomy or leave the placenta in situ for spontaneous delivery is based on the extent of infiltration, the patient's hemodynamic status, and her desire to remain fertile. The high-risk of infection and severe hemorrhage must not be overlooked should conservative treatment be chosen. This situation requires prolonged close monitoring. [less ▲]Detailed reference viewed: 28 (5 ULg)
Analgésie péridurale obstétricale et lombalgie du post-partum: un lien de cause à effet?
CHARLIER, Vanessa ; Brichant, Géraldine ; DEWANDRE, Pierre-Yves et al
in Revue Médicale de Liège (2012), 67(1), 16-20
backache is a common problem in the general population. the prevalence of backpain is increased during pregnancy and after delivery. early studies have suggested that labor epidural analgesia might be ... [more ▼]
backache is a common problem in the general population. the prevalence of backpain is increased during pregnancy and after delivery. early studies have suggested that labor epidural analgesia might be associated with an increased incidence of backache in the postpartum period. However, these initial studies were retrospective and their design included several methodological deficiencies. All the prospective studies published afterwards (prospective cohort studies and 3 ran- domized controlled trials) yield the same result : there is no relationship between labor epidural analgesia and long-term postpartum backpain. pregnant women must be aware of this in order to make an informed and appropriate choice about labor epidural analgesia, the most effective technique for intra- partum pain relief. [less ▲]Detailed reference viewed: 145 (10 ULg)
Insuffisance ovarienne prématurée : de la génétique à la clinique
; Foidart, Jean-Michel ; NISOLLE, Michelle et al
in Revue Médicale de Liège (2012), 67(7-8), 413-419
L’Insuffisance Ovarienne Prématurée (IOP) est une pathologie dont la présentation clinique est complexe. Elle survient chez 1% des femmes avant 40 ans, 0,1% avant 30 ans. Les causes sont multiples : les ... [more ▼]
L’Insuffisance Ovarienne Prématurée (IOP) est une pathologie dont la présentation clinique est complexe. Elle survient chez 1% des femmes avant 40 ans, 0,1% avant 30 ans. Les causes sont multiples : les anomalies génétiques, les maladies auto-immunes, les atteintes ovariennes iatrogènes secondaires à la chirurgie, radiothérapie, chimiothérapie, aux facteurs environnementaux tels que les virus, les toxines, le tabac, et aux facteurs métaboliques. Cependant, dans la majorité des cas, l’étiologie de l’IOP est idiopathique. [less ▲]Detailed reference viewed: 26 (6 ULg)