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See detailMatrix metalloproteinase-2 governs lymphatic vessel formation as an interstitial collagenase.
Detry, Benoît ULg; Erpicum, Charlotte ULg; Paupert, Jenny ULg 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 ▲]

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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 detailIsoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation
Labied, Soraya ULg; Delforge, Yves ULg; Blacher, Silvia ULg et al

in Journal of Assisted Reproduction & Genetics (2012), 28(11), 1009

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See detailDoes vascular endothelial growth factor improve ovarian tissue recovery after cryopreservation?
Henry, Laurie ULg; Fransolet, Maïté ULg; Labied, Soraya ULg et al

in Giornale italiano di obstetricia e gynecologia (2012)

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See detailBone Marrow-derived Myofibroblasts Are the Providers of Pro-invasive Matrix Metalloproteinase 13 in Primary Tumor.
Lecomte, Julie ULg; Masset, Anne; Blacher, Silvia ULg et al

in Neoplasia : An International Journal for Oncology Research (2012), 14(10), 943-51

Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes ... [more ▼]

Carcinoma-associated fibroblasts are key contributors of the tumor microenvironment that regulates carcinoma progression. They consist of a heterogeneous cell population with diverse origins, phenotypes, and functions. In the present report, we have explored the contribution of bone marrow (BM)-derived cells to generate different fibroblast subsets that putatively produce the matrix metalloproteinase 13 (MMP13) and affect cancer cell invasion. A murine model of skin carcinoma was applied to mice, irradiated, and engrafted with BM isolated from green fluorescent protein (GFP) transgenic mice. We provide evidence that one third of BM-derived GFP(+) cells infiltrating the tumor expressed the chondroitin sulfate proteoglycan NG2 (pericytic marker) or alpha-smooth muscle actin (alpha-SMA, myofibroblast marker), whereas almost 90% of Thy1(+) fibroblasts were originating from resident GFP-negative cells. MMP13producing cells were exclusively alpha-SMA(+) cells and derived from GFP(+) BM cells. To investigate their impact on tumor invasion, we isolated mesenchymal stem cells (MSCs) from the BM of wild-type and MMP13-deficient mice. Wild-type MSC promoted cancer cell invasion in a spheroid assay, whereas MSCs obtained from MMP13-deficient mice failed to. Our data support the concept of fibroblast subset specialization with BM-derived alpha-SMA(+) cells being the main source of MMP13, a stromal mediator of cancer cell invasion. [less ▲]

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See detailEffect of CO2 activation of carbon xerogels on the adsorption of methylene blue
Páez Martínez, Carlos ULg; Contreras, M. S.; Léonard, Angélique ULg et al

in Adsorption (2012), 18(3-4), 199-211

The effect of physical activation with CO2 of carbon xerogels, synthesized by pyrolysis of a resorcinolformaldehyde aqueous gel, on the adsorption capacities of Methylene Blue (MB) was studied. The ... [more ▼]

The effect of physical activation with CO2 of carbon xerogels, synthesized by pyrolysis of a resorcinolformaldehyde aqueous gel, on the adsorption capacities of Methylene Blue (MB) was studied. The activation with CO2 lead to carbon materials with micropore volumes ranging from 0.28 to 0.98 cm³/g -1 C. MB-adsorption isotherm studies showed that the increase of micropore volume and corresponding surface area led to: (i) a significant improvement in the capacity of MB-adsorption at monolayer coverage, from 212 to 714 mgg -1 C, and (ii) an increase of the binding energy related to Langmuir isotherm constant up to 45 times greater than those of commercial microporous activated carbons used as reference (NORIT R2030, CALGON BPL and CALGON NC35). It is proposed that the increase of the binding energy results from chemical cleaning of the O-groups onto carbon surface as a consequence of CO2-activation, increasing the π-π interaction between MB and graphene layers of the carbon xerogels. Finally, a series of batch kinetics were performed to investigate the effect of CO2-activation conditions on the mechanism of MB-adsorption. Experimental data were fitted using pseudo-first-order, pseudo-second-order and intraparticle diffusion kinetic models. From pseudo-second-order kinetic model, one observes an increase in the initial rate of MB-adsorption from 0.019 to 0.0565 min -1, by increasing the specific surface area from 630 to 2180 m²/g -1 C via CO2-activation. Depending on the activation degree of the carbons, two different mechanisms control the MB-adsorption rate: (i) at low activation degree, the intraparticle diffusion is the rate-limiting phenomenon, whereas (ii) at high activation degree, the reactions occurring at the solid/liquid interface are the rate-limiting steps. © 2012 Springer Science+Business Media, LLC. [less ▲]

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See detailThe proteolytic activity of MT4-MMP is required for its proangiogenic and pro-metastatic promoting effects
Host, Lorin; Paye, Alexandra ULg; Detry, Benoît ULg et al

in International Journal of Cancer = Journal International du Cancer (2012), 131(7), 1537-1548

MT4-MMP expression in breast adenocarcinoma stimulates tumor growth and metastatic spreading to the lung. However whether these pro-tumorigenic and pro-metastatic effects of MT4-MMP are related to a ... [more ▼]

MT4-MMP expression in breast adenocarcinoma stimulates tumor growth and metastatic spreading to the lung. However whether these pro-tumorigenic and pro-metastatic effects of MT4-MMP are related to a proteolytic action is not known yet. Through site directed mutagenesis MT4-MMP has been inactivated in cancer cells through Glutamic acid 249 substitution by Alanine in the active site. Active MT4-MMP triggered an angiogenic switch at day 7 after tumor implantation and drastically accelerated subcutaneous tumor growth as well as lung colonization in RAG -/- mice. All these effects were abrogated upon MT4-MMP inactivation. In sharp contrast to most MMPs being primarily of stromal origin, we provide evidence that tumor-derived MT4-MMP, but not host-derived MT4-MMP contributes to angiogenesis. A genetic approach using MT4-MMP-deficient mice revealed that the status of MT4-MMP produced by host cells did not affect the angiogenic response. Despite of this tumor intrinsic feature, to exert its tumor promoting effect, MT4-MMP requires a permissive microenvironment. Indeed, tumor-derived MT4-MMP failed to circumvent the lack of an host angio-promoting factor such as lasminogen activator inhibitor (PAI-1). Overall, our study demonstrates the key contribution of MT4-MMP catalytic activity in the tumor compartment, at the interface with host cells. It identifies MT4-MMP as a key intrinsic tumor cell determinant that contributes to the elaboration of a permissive microenvironment for metastatic dissemination [less ▲]

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See detailAbnormal vascular architecture at the placental-maternal interface in placenta increta
CHANTRAINE, Frédéric ULg; Blacher, Silvia ULg; Berndt, Sarah et al

in American Journal of Obstetrics and Gynecology (2012), 207(3), 1881-9

Objective The objective of the study was to characterize the vascular architecture at the placental-maternal interface in pregnancies complicated by placenta increta and normal pregnancies. Study Design ... [more ▼]

Objective The objective of the study was to characterize the vascular architecture at the placental-maternal interface in pregnancies complicated by placenta increta and normal pregnancies. Study Design Vessel numbers and cross-section area density and spatial and area distributions in 13 placenta-increta placental beds were compared with 9 normal placental beds using computer-assisted image analysis of whole-slide CD31 immunolabeled sections. Results The total areas occupied by vessels in normal and placenta-increta placental beds were comparable, but vessels were significantly sparser and larger in the latter. Moreover, placenta-increta–vessel distributions (area and distance from the placental–myometrial junction) were more heterogeneous. Conclusion Size and spatial organization of the placenta-increta vascular architecture at the placental-maternal interface differed from normal and might partially explain the severe hemorrhage observed during placenta-increta deliveries. [less ▲]

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See detailAdsorption of methylene blue on activated carbon xerogels
Páez Martínez, Carlos ULg; Contreras, Maria Soledad; Léonard, Angélique ULg et al

Poster (2011, November 30)

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See detailThe Antiangiogenic 16K Prolactin Impairs Functional Tumor Neovascularization by Inhibiting Vessel Maturation
Nguyen, Ngoc-Quynh-Nhu ULg; Castermans, Karolien; Berndt, Sarah et al

in PLoS ONE (2011), 6(11), 27318-27318

Background: Angiogenesis, the formation of new blood vessels from existing vasculature, plays an essential role in tumor growth, invasion, and metastasis. 16K hPRL, the antiangiogenic 16-kDa N-terminal ... [more ▼]

Background: Angiogenesis, the formation of new blood vessels from existing vasculature, plays an essential role in tumor growth, invasion, and metastasis. 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. Methodology/Principal Findings: 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. Conclusions/Significance: Taken together, our data show that 16K hPRL impairs functional tumor neovascularization by inhibiting vessel maturation and for the first time that an endogenous antiangiogenic agent disturbs Notch signaling. 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 detailInhibition of Experimental Corneal Neovascularization by Sunitinib Administration
Detry, Benoît ULg; BLACHER, Silvia ULg; Erpicum, Charlotte ULg et al

Poster (2011, October)

Cornea engraftment is the most common organ transplantation practiced around the world. The cornea is totally devoid of blood or lymphatic vessels, except in a peripheral zone called the limbus. This ... [more ▼]

Cornea engraftment is the most common organ transplantation practiced around the world. The cornea is totally devoid of blood or lymphatic vessels, except in a peripheral zone called the limbus. This property, named “corneal angiogenic privilege”, is conserved among all mammals to maintain cornea transparency and optimal visual acuity. In pathological conditions such as trauma, infections or hypoxia, blood and lymphatic vessels can grow into the avascular cornea, reducing visual acuity. In case of keratoplasty, it also considerably increases the risk of cornea graft rejection and is so considered as a high-risk keratoplasty. Treatments improving cornea survival after transplantation need to be developed, notably aiming at blocking corneal neovascularization. Here, we evaluated the efficacy of Sunitinib, a broad-spectrum tyrosine kinase receptor inhibitor, to reduce experimental corneal neovascularization. Cornea vascularization was induced by thermal cauterization applied in the center of C57Bl6 mice cornea, daily feeded with 40mg/kg Sunitinib or vehicule. Corneas were immunolabeled as whole mounts for CD31 and Lyve-1 to evidence blood and lymphatic vessels, 7, 11 and 17 days after cauterization. Whole mount pictures were analyzed by computer-assisted quantification, and relative vascular area, end-point density, node density, length density and maximal length of the vessels were determined to finely characterize blood and lymphatic vascular networks. We observed an inhibition of angiogenesis after 17 days in Sunitinib treated mice, where blood vessel relative surface, end-point density, branching density and length density were 1.8-fold decreased. Maximum length of blood vessels was also significantly reduced in the Sunitinib treated group at days 11 and 17. Lymphangiogenesis was strongly inhibited from day 6 to day 17 after cauterization where all parameters, except maximum length of lymphatic vessels, were significantly decreased. In case of transient Sunitinib administration (feeding during the 7 first days), we did not observe any reduction in the extent of blood or lymphatic networks developing 21 days after lesion induction. In vitro experimentations using the aortic and lymphatic ring assays showed a strong angiogenesis inhibition induced by Sunitinib while lymphangiogenesis was not inhibited. Our results show that the use of Sunitinib can strongly affect corneal neovascularisation and could enter in early treatment of such eye lesions to avoid vision loss and risk of cornea graft rejection. However, a punctual use of such tyrosine kinase inhibitor is not sufficient to stem neovascular reaction. In vitro experimentations show strong angiogenesis inhibition but normal lymphangiogenesis, suggesting indirect inhibitory effect of Sunitinib on corneal lymphangiogenesis. [less ▲]

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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 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 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 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 detailEffect of the activating agent on physico-chemical and electrical properties of activated carbon cloths developed from a novel cellulosic precursor
Ramos, ME; Bonelli, PR; Blacher, Silvia ULg et al

in Colloids and Surfaces A : Physicochemical and Engineering Aspects (2011), 378(1-3), 87-93

Different chemical reagents (phosphoric acid, boric acid, ammonium citrate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate and trisodium phosphate) were employed ... [more ▼]

Different chemical reagents (phosphoric acid, boric acid, ammonium citrate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate and trisodium phosphate) were employed to develop activated carbon cloths (ACC) by chemical activation of a lyocell precursor, in an attempt to explore their effect on main physico-chemical characteristics and electrical behaviour of the resulting ACC. The activating agent markedly influenced yield, elemental composition, and textural properties of the ACC. The ACC obtained with phosphoric and boric acids were essentially microporous, whereas those developed with the other reagents presented mesoporosity development. Phosphoric acid-derived samples showed the highest specific surface area (976 m2/g). The results also highlight the relevance of correcting the external surface adsorption in order to obtain reliable estimates of micropore volume. All the ACC were electrically conductive, their resistivity being also strongly dependent on the nature of the activating agent. The electrical resistivity of the ACC obtained with all the phosphorous compounds was successfully correlated with their C/H ratio and micropore volume [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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