References of "Erpicum, Charlotte"
     in
Bookmark and Share    
Full Text
See detailLymphangiogenesis and extracellular matrix remodeling
Erpicum, Charlotte ULg; Detry, Benoît ULg; Paupert, Jenny ULg et al

Conference (2013, January 28)

Detailed reference viewed: 28 (6 ULg)
Full Text
Peer Reviewed
See detailSunitinib inhibits inflammatory corneal lymphangiogenesis.
Detry, Benoît ULg; Blacher, Silvia ULg; Erpicum, Charlotte ULg 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: 19 (6 ULg)
Full Text
Peer Reviewed
See detailTargeting a single function of the multifunctional matrix metalloprotease MT1-MMP. Impact on lymphangiogenesis.
Ingvarsen, Signe; Porse, Astrid; Erpicum, Charlotte ULg et al

in Journal of Biological Chemistry (2013), sous presse

The group of matrix metalloproteases (MMPs) is responsible for multiple processes of extracellular matrix remodeling in the healthy body but also for matrix and tissue destruction during cancer invasion ... [more ▼]

The group of matrix metalloproteases (MMPs) is responsible for multiple processes of extracellular matrix remodeling in the healthy body but also for matrix and tissue destruction during cancer invasion and metastasis. The understanding of the contributions from each individual MMP, both in healthy and pathological events, has been complicated by the lack of specific inhibitors and the fact that some of the potent MMPs are multifunctional enzymes. These factors have also hampered the setup of therapeutic strategies targeting MMP activity. A tempting target is the membrane-associated MT1-MMP which has well-documented importance in matrix degradation but which takes part in more than one pathway in this regard. In this report, we describe the selective targeting of a single function of this enzyme by means of a specific monoclonal antibody against MT1-MMP, raised in an MT1-MMP knock-out mouse. The antibody blocks the enzyme ability to activate proMMP-2 without interfering with the collagenolytic function or the general proteolytic activity of MT1-MMP. Using this antibody, we have shown that the MT1-MMP-catalyzed activation of proMMP- 2 is involved in the outgrowth of cultured lymphatic endothelial cells in a collagen matrix in vitro, as well as in lymphatic vessel sprouting assayed ex vivo. This is the first example of the complete inactivation of a single function of a multifunctional MMP and the use of this strategy to pursue its role. [less ▲]

Detailed reference viewed: 15 (5 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 147 (63 ULg)
Full Text
Peer Reviewed
See detailModelling Lymphatic and blood capillary patterning
Bruyere, Françoise; Maillard, Catherine ULg; Erpicum, Charlotte ULg et al

in Davies, Jamie (Ed.) Replacing Animal Models, a practical guide to creating and using culture-based biomimetic alternatives (2012)

Angiogenesis and lymphangiogenesis, the formation of new blood or lymphatic vessels from preexisting ones, are important biological processes associated with diverse physiological processes, tissue repair ... [more ▼]

Angiogenesis and lymphangiogenesis, the formation of new blood or lymphatic vessels from preexisting ones, are important biological processes associated with diverse physiological processes, tissue repair and pathologies, such as cancer. Much progress has been made in recent years in identifying molecules specifically expressed on blood and lymphatic vessels and in the setting up of models of angiogenesis and lymphangiogenesis. In this review, we describe the most common in vitro models of (lymph)angiogenesis that have proven suitable for investigating angiogenic and lymphatic biology, and offer alternatives to animal experimentation. Their rationales, limitations and applications in biomedical research are discussed. A special emphasis will be given on ring assays that provide excellent recapitulation of various steps of (lymph)angiogenesis. The aortic ring assay has become the most widely used methods to study in vitro angiogenesis, and the recently set up lymphatic ring assay provides the opportunity to extend the in vitro studies to lymphangiogenesis. [less ▲]

Detailed reference viewed: 18 (7 ULg)
Peer Reviewed
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 ▲]

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailDigging deeper into lymphatic vessel formation in vitro and in vivo
Detry, Benoît ULg; Bruyère, F.; Erpicum, Charlotte ULg et al

in BMC Cell Biology (2011), 12

Background Abnormal lymphatic vessel formation (lymphangiogenesis) is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays ... [more ▼]

Background Abnormal lymphatic vessel formation (lymphangiogenesis) is associated with different pathologies such as cancer, lymphedema, psoriasis and graft rejection. Lymphatic vasculature displays distinctive features than blood vasculature, and mechanisms underlying the formation of new lymphatic vessels during physiological and pathological processes are still poorly documented. Most studies on lymphatic vessel formation are focused on organism development rather than lymphangiogenic events occurring in adults. We have here studied lymphatic vessel formation in two in vivo models of pathological lymphangiogenesis (corneal assay and lymphangioma). These data have been confronted to those generated in the recently set up in vitro model of lymphatic ring assay. Ultrastructural analyses through Transmission Electron Microscopy (TEM) were performed to investigate tube morphogenesis, an important differentiating process observed during endothelial cell organization into capillary structures. [less ▲]

Detailed reference viewed: 59 (17 ULg)
Peer Reviewed
See detailInvolvement of z-MMP-2 in Zebrafish lymphangiogenesis
Paupert, Jenny ULg; Pendeville, Hélène; Detry, Benoît ULg et al

Poster (2011, May)

Detailed reference viewed: 6 (0 ULg)
Peer Reviewed
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 ▲]

Detailed reference viewed: 12 (1 ULg)
Peer Reviewed
See detailInvolvement of z-MMP-2 in Zebrafish lymphangiogenesis
Paupert, Jenny ULg; Pendeville, Hélène; Detry, Benoît ULg et al

Conference (2011)

Detailed reference viewed: 15 (2 ULg)