References of "Noël, Agnès"
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See detailMT-MMPs as regulators of vessel stability associated with angiogenesis
Sounni, Nor Eddine ULg; Paye, Alexandra ULg; Host, Lorin et al

in Frontiers in Pharmacology of Anti-Cancer Drugs (2011), 2:111

The development of vascular system depends on the coordinated activity of a number of distinct families of molecules including growth factors and their receptors, cell adhesion molecules, extracellular ... [more ▼]

The development of vascular system depends on the coordinated activity of a number of distinct families of molecules including growth factors and their receptors, cell adhesion molecules, extracellular matrix (ECM) molecules, and proteolytic enzymes. Matrix metalloproteases (MMPs) are a family of ECM degrading enzymes required for both physiological and pathological angiogenesis. Increasing evidence, point to a direct role of membrane type-MMPs (MT-MMPs) in vascular system stabilization, maturation, and leakage. Our understanding of the nature of MT-MMP interaction with extracellular and cell surface molecules and their multiple roles in vessel walls and perivascular stroma may provide new insights into mechanisms underlying vascular cell-ECM interactions and cell fate decisions in pathological conditions. Regulation of vascular leakage by MT-MMP interactions with the ECM could also lead to novel targeting opportunities for drug delivery in tumor. This review will shed lights on the emerging roles of MT1-MMP and MT4-MMP in vascular system alterations associated with cancer progression. [less ▲]

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See detailInvolvement of z-MMP-2 in Zebrafish lymphangiogenesis
Paupert, Jenny ULg; Pendeville, Hélène; Detry, Benoît ULg et al

Poster (2011, May)

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See detailThe antiangiogenic 16K prolactin disturbs functional tumor neovascularization by affecting vessel maturation
Nguyen, Ngoc-Quynh-Nhu ULg; Castermans, Karolien; Berndt, Sarah et al

Poster (2011, May)

16K hPRL, the antiangiogenic 16-kDa N-terminal fragment of human prolactin was shown to prevent tumor growth and metastasis by modifying tumor vessel morphology. Here we investigated the effect of 16K ... [more ▼]

16K hPRL, the antiangiogenic 16-kDa N-terminal fragment of human prolactin was shown to prevent tumor growth and metastasis by modifying tumor vessel morphology. Here we investigated the effect of 16K hPRL on tumor vessel maturation and on the related signaling pathways. We show that 16K hPRL treatment leads, in a murine B16-F10 tumor model, to a dysfunctional tumor vasculature with reduced pericyte coverage, and disruption of the PDGF-B/PDGFR-B, Ang/Tie2, and Delta/Notch pathways. In an aortic ring assay, 16K hPRL impairs endothelial cell and pericyte outgrowth from the vascular ring. In addition, 16K hPRL prevents pericyte migration to endothelial cells. This event was independent of a direct inhibitory effect of 16K hPRL on pericyte viability, proliferation, or migration. In endothelial cell-pericyte cocultures, we found 16K hPRL to disturb Notch signaling, this being the first time such an effect is observed with an endogenous antiangiogenic agent. These findings provide new insights into the mechanisms of 16K hPRL action and highlight its potential for use in anticancer therapy. [less ▲]

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See detailMir-146a : A new angiostatic miRNA with tumor-suppressive properties
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, March)

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See detailMiR-146a an angiostatic miRNA elevated in peripartum cardiomyopathy
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, March)

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See detailMiR-146a: an angiostatic miRNA with tumor-suppressive properties
Halkein, Julie ULg; Bovy, Nicolas ULg; Castermans, Karolien et al

Poster (2011, February)

Detailed reference viewed: 17 (7 ULg)
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See detailMiR-146a an angiostatic miRNA elevated in peripartum cardiomyopathy
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, February)

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See detailmicroRNA-21 Exhibits Anti-Angiogenic Function by Targeting RhoB Expression in Endothelial Cells
Sabatel, Céline; Malvaux, Ludovic; Bovy, Nicolas ULg et al

Poster (2011, February)

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See detailNovel HDAC/DNMT Twin inhibitors interfere with angiogenesis
Shiva Shankar, Thammadihalli Veerasangaiah ULg; Sulka, Béatrice ULg; Blacher, Silvia ULg et al

Poster (2011, January 31)

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA ... [more ▼]

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA methyltransferases (DNMT) inhibitors are potent anti-angiogenic compounds. Though combination of HDAC and DNMT inhibitors are now being examined in clinical trials of hematological malignancies, little work has been done to understand the effect of this combination on physiological and tumoral angiogenesis. We have designed and tested a family of twin drugs with intrinsic HDAC and DNMT inhibitory activities in relevant models of angiogenesis in vitro (Human Umbilical Vein Endothelial Cells – HUVEC and aortic ring) and in vivo (chick chorioallantoic membrane and Zebrafish). We have identified a lead compound having quantifiable anti-angiogenic effect without cytotoxicity affecting global histone acetylation and DNA methylation levels. In order to elucidate its anti-angiogenic mechanism, we characterized gene expression pattern simultaneously with the methylation profile of HUVEC cells treated with the lead compound and reference epigenetic modulators. This approach based on parallel microarray analyses permitted us to underscore a list of genes exclusively affected by the lead compound but not by other HDAC or DNMT inhibitors. These genes were then analyzed using the Ingenuity Pathway software revealing potential involvement of a subset of genes in angiogenesis. Our present aim is to validate the expression levels of a series of genes with respect to epigenetic mechanisms (histone modifications and DNA methylation). Finally, the biological relevance of the target genes will be explored by RNA silencing. Hence, we are using these novel epigenetic modulators as a tool to understand the regulatory mechanism of angiogenesis and to develop effective approaches to treat cancer. [less ▲]

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See detaildoes neoadjuvant radiotherapy promote tumor dissemination ,
Leroi, Natacha ULg; boujouf, Sarah; COUCKE, Philippe ULg et al

Poster (2011, January)

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See detailMiR-146a an angiostatic miRNA elevated in peripartum cardiomyopathy
Halkein, Julie ULg; Castermans, Karolien; Malvaux, Ludovic et al

Poster (2011, January)

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See detailNovel HDAC/DNMT Twin Inhibitors Interfere with Angiogenesis
Shiva Shankar, Thammadihalli Veerasangaiah ULg; Sulka, Béatrice ULg; Blacher, Silvia ULg et al

Poster (2011)

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA ... [more ▼]

DNA methylation and histone deacetylation are two key epigenetic modifications that play central role in regulation of gene expression. Several studies have shown that histone deacetylases (HDAC) and DNA methyltransferases (DNMT) inhibitors are potent anti-angiogenic compounds. Though combination of HDAC and DNMT inhibitors are now being examined in clinical trials of hematological malignancies, little work has been done to understand the effect of this combination on physiological and tumoral angiogenesis. We have designed and tested a family of twin drugs with intrinsic HDAC and DNMT inhibitory activities in relevant models of angiogenesis in vitro (Human Umbilical Vein Endothelial Cells – HUVEC and aortic ring) and in vivo (chick chorioallantoic membrane and Zebrafish). We have identified a lead compound having quantifiable anti-angiogenic effect without cytotoxicity affecting global histone acetylation and DNA methylation levels. In order to elucidate its anti-angiogenic mechanism, we characterized gene expression pattern simultaneously with the methylation profile of HUVEC cells treated with the lead compound and reference epigenetic modulators. This approach based on parallel microarray analyses permitted us to underscore a list of genes exclusively affected by the lead compound but not by other HDAC or DNMT inhibitors. These genes were then analyzed using the Ingenuity Pathway software revealing potential involvement of a subset of genes in angiogenesis. Our present aim is to validate the expression levels of a series of genes with respect to epigenetic mechanisms (histone modifications and DNA methylation). Finally, the biological relevance of the target genes will be explored by RNA silencing. Hence, we are using these novel epigenetic modulators as a tool to understand the regulatory mechanism of angiogenesis and to develop effective approaches to treat cancer. [less ▲]

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See detailEnhanced Activity of Meprin-a, a Pro-Migratory and Pro-Angiogenic Protease, in Colorectal Cancer
Lottaz, Daniel; Maurer, Christoph A; Noël, Agnès ULg et al

in PLoS ONE (2011), 6(11), 26450

Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is ... [more ▼]

Meprin-α is a metalloprotease overexpressed in cancer cells, leading to the accumulation of this protease in a subset of colorectal tumors. The impact of increased meprin-α levels on tumor progression is not known. We investigated the effect of this protease on cell migration and angiogenesis in vitro and studied the expression of meprin-α mRNA, protein and proteolytic activity in primary tumors at progressive stages and in liver metastases of patients with colorectal cancer, as well as inhibitory activity towards meprin-α in sera of cancer patient as compared to healthy controls. We found that the hepatocyte growth factor (HGF)- induced migratory response of meprin-transfected epithelial cells was increased compared to wild-type cells in the presence of plasminogen, and that the angiogenic response in organ-cultured rat aortic explants was enhanced in the presence of exogenous human meprin-α. In patients, meprin-α mRNA was expressed in colonic adenomas, primary tumors UICC (International Union Against Cancer) stage I, II, III and IV, as well as in liver metastases. In contrast, the corresponding protein accumulated only in primary tumors and liver metastases, but not in adenomas. However, liver metastases lacked meprin-α activity despite increased expression of the corresponding protein, which correlated with inefficient zymogen activation. Sera from cancer patients exhibited reduced meprin-α inhibition compared to healthy controls. In conclusion, meprin-α activity is regulated differently in primary tumors and metastases, leading to high proteolytic activity in primary tumors and low activity in liver metastases. By virtue of its pro-migratory and pro-angiogenic activity, meprin-α may promote tumor progression in colorectal cancer. [less ▲]

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See detailLymphangiogenesis and extracellular matrix remodeling
Erpicum, Charlotte ULg; Detry, Benoît ULg; Paupert, Jenny ULg et al

Poster (2011)

Lymphangiogenesis, the formation of new lymphatic vessels from preexisting ones, is an important biological process associated with diverse pathologies, such as metastatic dissemination and graft ... [more ▼]

Lymphangiogenesis, the formation of new lymphatic vessels from preexisting ones, is an important biological process associated with diverse pathologies, such as metastatic dissemination and graft rejection. Our laboratory has previously identified MMP2 as a key regulator of lymphangiogenesis in vitro and in vivo. However, the exact function of MMP2 in this process is yet unknown. The present work aims at elucidating the mechanisms of MMP2 action during lymphangiogenesis. MMP2 could either act as a growth factor activator or as a regulator of matrix remodeling. To address this question, we studied the effect of MMP2 on lymphangiogenesis in an novel in vitro model of sprouting cells from small aggregates (spheroids) seeded in a collagen gel. In this model, quantification of the lymphangiogenic response is performed through computerized methods allowing the measurement of the distance of migration, but also the evaluation of how the cell are migrating. We evaluated the impact of MMP2 blockage through the use of physiological (TIMP2) or chemical inhibitors or by downregulating its expression with specific siRNA. The importance of extracellular matrix composition is evaluated by embedding these spheroids into different matrices (matrigel versus collagen; pepsinized collagen versus native collagen; different collagen concentrations). Our results reveal a modification of cell migration through collagen gel after MMP2 inhibition. The utilization of DQ collagen and microscopy refractance confirmed the importance of MMP2 collagenoyitic activity for lymphangiogenesis. [less ▲]

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See detailInvasion and metastatic dissemination in breast cancer: mechanisms
Noël, Agnès ULg; Gilles, Christine ULg; Foidart, Jean-Michel ULg

in Revue Médicale de Liège (2011), 66(5-6), 274-278

Metastases formation is a complex process involving genetic and epigenetic modifications leading to several molecular pathway dysfunctions and alterations in the production and fonction of a panel of ... [more ▼]

Metastases formation is a complex process involving genetic and epigenetic modifications leading to several molecular pathway dysfunctions and alterations in the production and fonction of a panel of molecular mediators. Recent studies have shed light on the importance of multiple interactions occuring between tumor cells and host cells involved in the elaboration of a microenvironment permissive for tumor cell survival and growth. These tumor-host interactions are decisive, not only in the primary tumor, but also in secondary sites colonized by tumor cells. Cancer appears more and more as a sytemic disease in which tumor cell is one of the pawn in the game. System of defense are rapidly overwhelmed and tumor cells hijack host cells to promote their dissemination that likely occurs at earlier stages than initially anticipated. In the present review, we describe the novel concepts of metastases formation based on recent transcriptomic analyses and new insights acquired on the tumor microenvironment in the primary tumor and in secondary foci. [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 detailTransient reduction of placental angiogenesis in PAI-1 deficient mice
Labied, Soraya ULg; Blacher, Silvia ULg; Carmeliet, P. et al

in Physiological Genomics (2011), 43(4), 188-98

Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and foetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently ... [more ▼]

Murine placentation is associated with the invasion of maternal endometrium by trophoblasts and an extensive maternal and foetal angiogenesis. Plasminogen activator inhibitor-1 (PAI-1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at 10.5-11.5 day post-coitum (dpc). Knowing the key contribution of PAI-1 in the regulation of angiogenesis, we have now analyzed the consequence of PAI-1 deficiency on murine placentation. Morphological and quantitative computer-assisted image analysis revealed abnormal placental morphology in PAI-1 (-/-) mice at 10.5 and 12.5 dpc. At 10.5 dpc, the genetic ablation of PAI-1 resulted in a transient reduction of both maternal and foetal vascularizations in the placenta and increased trophoblast cell density. This was associated with a poorer development of the labyrinth and an extension of the decidua. A larger spongiotrophoblast layer appeared at 12.5 dpc in PAI-1 deficient mice. Placental morphology was normalized at 14,5 dpc. Microarray analyses performed on laser capture microdissected labyrinths revealed that 46 genes were differentially expressed at 10.5 dpc between the two genotypes. However, only 11 genes were still differently modulated at 14.5 dpc when normalization of placental morphology had take place. This transcriptomic profiling highlighted a dysregulation in the expression of placenta-related cathepsin family members. All together our data provide evidence for a transient impaired placental morphology in PAI-1-deficient mice which is then normalized leading to normal embryonic development. [less ▲]

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See detailWhole Slide Quantification of Stromal Lymphatic Vessel Distribution and Peritumoral Lymphatic Vessel Density in Early Invasive Cervical Cancer: A Method Description
Balsat, Cédric ULg; Blacher, Silvia ULg; Signolle, Nicolas et al

in ISRN Obstetrics and Gynecology (2011), 2011

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional ... [more ▼]

Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive marker for the presence of lymph node metastases in cervical cancer. However, when LVD quantification relies on conventional optical microscopy and the hot spot technique, interobserver variability is significant and yields inconsistent conclusions. In this work, we describe an original method that applies computed image analysis to whole slide scanned tissue sections following immunohistochemical lymphatic vessel staining. This procedure allows to determine an objective LVD quantification as well as the lymphatic vessel distribution and its heterogeneity within the stroma surrounding the invasive tumor bundles. The proposed technique can be useful to better characterize lymphatic vessel interactions with tumor cells and could potentially impact on prognosis and therapeutic decisions. [less ▲]

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See detailADAM-8, a metalloproteinase, drives acute allergen-induced airway inflammation
Paulissen, Geneviève ULg; Rocks, Natacha ULg; Guéders, Maud ULg et al

in European Journal of Immunology (2011), 41(2), 380-91

Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A Disintegrin And Metalloproteinases (ADAMs) displaying the ability to ... [more ▼]

Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A Disintegrin And Metalloproteinases (ADAMs) displaying the ability to cleave membrane-bound mediators or cytokines appear to be key mediators in various inflammatory processes. In the present study, we have investigated ADAM-8 expression and production in a mouse model of allergen-induced airway inflammation. In allergen-exposed animals, increased expression of ADAM-8 was found in the lung parenchyma and in dendritic cells purified from the lungs. The potential role of ADAM-8 in the development of allergen-induced airway inflammation was further investigated by the use of an anti-ADAM-8 antibody and ADAM-8 knock-out animals. We observed a decrease in allergen-induced acute inflammation both in BALF and the peribronchial area in anti-ADAM-8 antibody-treated mice and in ADAM-8 deficient mice (ADAM-8-/-) after allergen exposure. ADAM-8 depletion led to a significant decrease of the CD11c+ lung dendritic cells. We also report lower levels of CCL11 and CCL22 production in antibody-treated mice and ADAM-8-/- mice that might be explained by decreased eosinophilic inflammation and lower numbers of dendritic cells, respectively. In conclusion, ADAM-8 appears to favour allergen-induced acute airway inflammation by promoting dendritic cell recruitment and CCL11 and CCL22 production. [less ▲]

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