References of "Noël, Agnès"
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See detailRestricted expression of membrane type 1-matrix metalloproteinase by myofibroblasts adjacent to human breast cancer cells
Bisson, C.; Blacher, Silvia ULg; Polette, M. et al

in International Journal of Cancer = Journal International du Cancer (2003), 105(1), 7-13

The membrane type-1 matrix metalloproteinase (MT1-MMP), a protease originally identified in breast carcinoma, is characterized by its capacity to activate other MMPs (MMP-2 and MMP-13) and to degrade ... [more ▼]

The membrane type-1 matrix metalloproteinase (MT1-MMP), a protease originally identified in breast carcinoma, is characterized by its capacity to activate other MMPs (MMP-2 and MMP-13) and to degrade extracellular matrix. Our study was undertaken to localize and identify the MT1-MMP expressing cells in human breast adenocarcinomas. A textural analysis of images obtained by immunohistochemistry and in situ hybridization showed precisely the co-expression of alpha smooth muscle actin (alphaSM actin) and MT1-MMP in myofibroblasts. MT1-MMP expression is confined to myofibroblasts in close contact with tumor cells. In sharp contrast, the expression of MMP-2 was more widely distributed in both alphaSM actin positive and negative cells close to and at distance from cancer cell clusters. Our in vitro observations are consistent with the higher level of MT1-MMP expression and of MMP-2 activation observed in alphaSM actin positive fibroblasts derived from breast tumors, as compared to normal breast fibroblasts. Collectively, these results implicate myofibroblasts as major producer of MT1-MMP in breast cancer and emphasize the importance of stromal-epithelial cell interactions in their progression. [less ▲]

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See detail3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo
Kempen, I.; Papapostolou, D.; Thierry, N. et al

in British Journal of Cancer (2003), 88(7), 1111-1118

In search for new anticancer agents, we have evaluated the antiinvasive and antimigrative properties of recently developed synthetic coumarin derivatives among which two compounds revealed important ... [more ▼]

In search for new anticancer agents, we have evaluated the antiinvasive and antimigrative properties of recently developed synthetic coumarin derivatives among which two compounds revealed important activity: 3-chlorophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate and 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate, Both drugs were able to inhibit cell invasion markedly in a Boyden chamber assay, the bromo derivative being more potent than the reference matrix metalloprotease (MMP) inhibitor GI 129471. In vivo, tumour growth was reduced when nude mice grafted with HT 1080 or MDA-MB231 cells were treated i.p. 3 days week(-1) with the bromo coumarin derivative. These effects were not associated with the inhibition of urokinase, plasmin, MMP-2 or MMP-9. The mechanism of action of the drugs remains to be elucidated. However, these two coumarin derivatives may serve as new lead compounds of an original class of antitumour agents. [less ▲]

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See detailEffects of a progestogen on normal human breast epithelial cell apoptosis in vitro and in vivo
Desreux, Joëlle ULg; Kebers, F.; Noël, Agnès ULg et al

in Breast (Edinburgh, Scotland ) (2003), 12(2), 142-149

Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis ... [more ▼]

Many investigators have reported cyclic proliferation of normal human breast epithelial cells. A delicate balance between proliferation and apoptosis (programmed cell death) ensures breast homeostasis. Both the follicular and luteal phases of the menstrual cycle are characterized by proliferation, whereas apoptosis occurs only at the end of the latter phase. In this study, we observed that the withdrawal of a synthetic progestin (nomegestrol acetate or NOMAC), but not continuous treatment with it, induced apoptosis of normal human breast epithelial cells in vitro and in women who applied NOMAC gel to their breasts. Furthermore, this apoptotic response was specific to normal breast cells, since withdrawal of NOMAC did not induce apoptosis of tumoral T47D cells in vitro or of fibroadenoma cells in women. These observations open up new perspectives in the prevention of hyperplasia and breast cancer. (C) 2003 Elsevier Science Ltd. All rights reserved. [less ▲]

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See detailMice without uPA, tPA, or plasminogen genes are resistant to experimental choroidal neovascularization
Rakic, Jean-Marie ULg; Lambert, Vincent ULg; Munaut, Carine ULg et al

in Investigative Ophthalmology & Visual Science (2003), 44(4), 1732-1739

PURPOSE. To evaluate the presence and potential involvement of members of the plasminogen/plasminogen activator (Plg/PA) system in the exudative form of age-related macular degeneration (AMD). METHODS ... [more ▼]

PURPOSE. To evaluate the presence and potential involvement of members of the plasminogen/plasminogen activator (Plg/PA) system in the exudative form of age-related macular degeneration (AMD). METHODS. The expression of PA members mRNA was evaluated in human and experimental choroidal neovascularization (CNV) by RT-PCR. The presence and activity of PA was studied by immunofluorescence and in situ zymography. The influence of endogenous plasminogen (Plg), urokinase (uPA), tissue type plasminogen activator (tPA), and uPA receptor (uPAR) was explored in single-gene-deficient mice in a model of laser-induced CNV. RESULTS. Members of the Plg/PA system were present both in human and murine CNV. The absence of Pig, uPA, or tPA significantly decreased the development of experimental CNV compared with wild-type or uPAR-deficient mice. This effect could be attributable, partly to a modulation of matrix metalloproteinase activity, but also to an accumulation of fibrinogen-fibrin in the laser-induced wounds. CONCLUSIONS. Together with previous work done by the authors, this study indicates that choroidal neovascularization is extremely sensitive to the modulation of Plg/PA system activity. This may provide a new strategy for the treatment of exudative AMD. [less ▲]

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See detailRole of plasminogen activator-plasmin system in tumor angiogenesis
Rakic, Jean-Marie ULg; Maillard, Catherine ULg; Jost, M. et al

in Cellular and Molecular Life Sciences : CMLS (2003), 60(3), 463-473

New blood formation or angiogenesis has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization. Angiogenesis is associated ... [more ▼]

New blood formation or angiogenesis has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization. Angiogenesis is associated with important extracellular remodeling involving different proteolytic systems among which the plasminogen system plays an essential role. It belongs to the large serine proteinase family and can act directly or indirectly by activating matrix metalloproteinases or by liberating growth factors and cytokines sequestered within the extracellular matrix. Migration of endothelial cells is associated with significant upregulation of proteolysis and, conversely, immunoneutralization or chemical inhibition of the system reduces angiogenesis in vitro. On the other hand, genetically altered mice developed normally without overt vascular anomalies indicating the possibility of compensation by other proteases in vivo. Nevertheless, they have in some experimental settings revealed unanticipated roles for previously characterized proteinases or their inhibitors. In this review, the complex mechanisms of action of the serine proteases in pathological angiogenesis are summarized alongside possible therapeutic applications. [less ▲]

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See detailAdhesion of endometrial cells labeled with 111 Indium-tropolonate to peritoneum: a novel in vitro model to study endometriosis
Beliard, Aude ULg; Noël, Agnès ULg; Goffin, Frédéric ULg et al

in Fertility and Sterility (2003), 79(Suppl. 1), 724-729

Objective: To evaluate, in a new original in vitro assay, putative factors that could modulate the adhesion of endometrial cells to peritoneum. Design: Prospective, controlled in vitro study. Setting ... [more ▼]

Objective: To evaluate, in a new original in vitro assay, putative factors that could modulate the adhesion of endometrial cells to peritoneum. Design: Prospective, controlled in vitro study. Setting: Academic research laboratory. Patient(s): Fourteen nonmenopausal women undergoing hysterectomy or laparoscopy for benign gynecologic indication. Intervention(s): Endometrial cells obtained from women with regular cycles without endometriosis were labeled with (111)Indium and confronted in vitro with mouse peritoneum in the presence of various cytokines and/or antiadhesive compounds. Main Outcome Measure(s): Radioactivity in (111)Indium-labeled endometrial cells. Result(s): The adhesion of human endometrial cells to mouse peritoneum was increased by treatment with pro-inflammatory cytokines (interleukin IL-1 beta, IL-6, TNF alpha, TGF-beta1). Whereas heparan sulfate had no effect on cell adhesion, a gel of ferric hyaluronate (Intergel) was able to counteract the pro-adhesive effect of cytokines. Interestingly, the pretreatment of peritoneum with cytokines, 24 hours before cell seeding in the presence of the ferric hyaluronate gel, restored the cytokine-promoting effect on cell adhesion. Conclusion(s): Proinflammatory cytokines promote the in vitro peritoneal adhesion of endometrial cells. An antiadhesive hyaluronate gel used in clinics decreases the adhesion in a dose-dependent manner and reduces cytokine bioavailability. (Fertil Steril((R)) 2003;79(Suppl 1):724-9. (C) 2003 by American Society for Reproductive Medicine.). [less ▲]

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See detailMembrane type-1 matrix metalloproteinase and TIMP-2 in tumor angiogenesis
Sounni, Nor Eddine ULg; Janssen, M.; Foidart, Jean-Michel ULg et al

in Matrix Biology (2003), 22(1), 55-61

The matrix metalloproteinases (MMPs) constitute a multigene family of over 23 secreted and cell-surface associated enzymes that cleave or degrade various pericellular substrates. In addition to virtually ... [more ▼]

The matrix metalloproteinases (MMPs) constitute a multigene family of over 23 secreted and cell-surface associated enzymes that cleave or degrade various pericellular substrates. In addition to virtually all extracellular matrix (ECM) compounds, their targets include other proteinases, chemotactic molecules, latent growth factors, growth factor-binding proteins and cell surface molecules. The MMP activity is controlled by the physiological tissue inhibitors of MMPs (TIMPs). There is much evidence that MMPs and their inhibitors play a key role during extracellular remodeling in physiological situations and in cancer progression. They have other functions that promoting tumor invasion. Indeed, they regulate early stages of tumor progression such as tumor growth and angiogenesis. Membrane type MMPs (MT-MMPs) constitute a new subset of cell surface-associated MMPs. The present review will focus on MT1-MMP which plays a major role at least, in the ECM remodeling, directly by degrading several of its components, and indirectly by activating pro-MMP2. As our knowledge on the field of MT1-MMP biology has grown, the unforeseen complexities of this enzyme and its interaction with its inhibitor TIMP-2 have emerged, often revealing unexpected mechanisms of action. (C) 2003 Elsevier Science B.V/Intemational Society of Matrix Biology. All rights reserved. [less ▲]

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See detailVascular endothelial growth factor expression correlates with matrix metalloproteinases MT1-MMP, MMP-2 and MMP-9 in human glioblastomas.
Munaut, Carine ULg; Noël, Agnès ULg; Hougrand, Olivier ULg et al

in International Journal of Cancer = Journal International du Cancer (2003), 106(6), 848-55

Vascular endothelial growth factor (VEGF) is the major endothelial mitogen in central nervous system neoplasms and it is expressed in 64-95% of glioblastomas (GBMs). Tumour cells are the main source of ... [more ▼]

Vascular endothelial growth factor (VEGF) is the major endothelial mitogen in central nervous system neoplasms and it is expressed in 64-95% of glioblastomas (GBMs). Tumour cells are the main source of VEGF in GBMs whereas VEGF receptors (VEGFR-1, its soluble form sVEGFR-1, VEGFR-2 and neuropilin-1) are expressed predominantly by endothelial cells. Infiltrating tumour cells and newly-formed capillaries progress through the extracellular matrix by local proteolysis involving matrix metalloproteinases (MMPs). Recent studies have shown that VEGF expression and bioavailability can be modulated by MMPs. We reported previously that the expression of MT1-MMP in human breast cancer cells was associated with an enhanced VEGF expression. We used quantitative RT-PCR, Western blot, gelatin zymography and immunohistochemistry to study the expression of VEGF, VEGFR-1, VEGFR-2, sVEGFR-1, neuropilin-1, MT1-MMP, MMP-2, MMP-9 and TIMP-2 in 20 human GBMs and 5 normal brains. The expression of these MMPs was markedly increased in most GBMs with excellent correlation between mRNA and protein levels; activated forms of MMP-2 and MMP-9 were present in 8/18 and 7/18 of GBMs. A majority of GBMs (17/20) also expressed high levels of VEGF, as previously reported, with strong correlation between VEGF and MT1-MMP gene expression levels, and double immunostaining showed that VEGF and MT1-MMP peptides co-localize in tumour and endothelial cells. Our results suggest that the interplay between metalloproteinases and VEGF previously described in experimental tumours may also be operative in human GBMs. Because of its dual ability to activate MMP-2 and to up-regulate VEGF, MT1-MMP might be of central importance in the growth of GBMs and represent an interesting target for anti-cancer treatments. [less ▲]

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See detailEstrogens reduce the expression of YKL-40 in the retina: Implications for eye and joint diseases
Rakic, Jean-Marie ULg; Lambert, Vincent ULg; Deprez, Manuel ULg et al

in Investigative Ophthalmology & Visual Science (2003), 44(4), 1740-1746

PURPOSE. To identify modifications in the gene expression profile of the ocular posterior segment in ovariectomized (OVX) mice with and without substitutive estradiol therapy and to select differentially ... [more ▼]

PURPOSE. To identify modifications in the gene expression profile of the ocular posterior segment in ovariectomized (OVX) mice with and without substitutive estradiol therapy and to select differentially expressed genes that could be relevant to the natural history of human age-related macular degeneration (AMD). METHODS. Chorioretinal tissues from two groups of 25 treated and untreated OVX mice were analyzed by using cDNA array technology. The expression level of selected genes was confirmed in triplicate by RT-PCR and related to the estrogenic status of the animals. Expression of the YKL-40 gene was further investigated in intact or diseased human retinas and in a murine model of experimental choroidal neovascularization (CNV), using laser pressure catapulting. RESULTS. Of the approximately, 10,000 genes screened, only YKL-40 expression was significantly downregulated by 17-beta-estradiol. YKL-40 was expressed in intact human neural retina and in the RPE. The expression of YKL-40 was upregulated in experimental CNV and in neovascular membranes extracted from patients affected by the exudative form of AMD. CONCLUSIONS. These observations indicate that YKL-40 expression in the retina is modulated by serum levels of estradiol. This protein could be relevant to the development of AMD and is also a new mediator to take into account when evaluating the broad consequences of hormonal replacement therapy. [less ▲]

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See detailMMP-2 and MMP-9 synergize in promoting choroidal neovascularization
Lambert, Vincent ULg; Wielockx, B.; Munaut, Carine ULg et al

in FASEB Journal (2003), 17(15), 2290-2292

Matrix metalloproteinase 2 (MMP-2) and MMP-9 are increased in human choroidal neovascularization (CNV) occurring during the exudative most aggressive form of age-related macular degeneration (AMD), but ... [more ▼]

Matrix metalloproteinase 2 (MMP-2) and MMP-9 are increased in human choroidal neovascularization (CNV) occurring during the exudative most aggressive form of age-related macular degeneration (AMD), but their precise role and potential interactions remain unclear. To address the question of MMP-2 and MMP-9 functions, mice deficient in the expression of MMP-2 (MMP-2 KO), MMP-9 (MMP-9 KO), and both MMP-2 and MMP-9 (MMP-2,9 KO) with their corresponding wild-type mice (WT) underwent CNV induction by laser-induced rupture of the Bruch's membrane. Both the incidence and the severity of CNV were strongly attenuated in double deficient compared with single gene deficient mice or corresponding WT controls. The reduced neovascularization was accompanied by fibrinogen/fibrin accumulation. Furthermore, overexpression of the endogenous MMP inhibitors TIMP-1 or TIMP-2 (delivered by adenoviral vectors) in WT mice or daily injection of a synthetic and gelatinase selective MMP inhibitor (Ro 26-2853) significantly decreased the pathological reaction. These findings suggest that MMP-2 and MMP-9 may cooperate in the development of AMD and that their selective inhibition represents an alternative strategy for the treatment of choroidal neovascularization. [less ▲]

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See detailQuantification of angiogenesis on the rat aortic ring assay.
Blacher, Silvia ULg; Devy, L.; Noël, Agnès ULg et al

in Image Analysis and Stereology (2003), 22

Image analysis is used to quantify angiogenesis on the rat aortic ring model. This technique allows to determine: (1) the aortic ring area and factor shape; (2) the number of microvessels, the total ... [more ▼]

Image analysis is used to quantify angiogenesis on the rat aortic ring model. This technique allows to determine: (1) the aortic ring area and factor shape; (2) the number of microvessels, the total number of branching, the maximal microvessel length and the number of microvessels in function of the distance to the aortic ring; (3) the total number of isolated fibroblast-like cells and the number of fibroblast-like cells in function of the distance to the aortic ring. We show that this method is suitable to quantify spontaneous angiogenesis as well as to analyse a complex microvascular network induced by vascular endothelial growth factor (VEGF). [less ▲]

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See detailPresence of alpha and beta estrogen receptors in human gingiva
Fraikin, N.; Munaut, Carine ULg; Lambert, Vincent ULg et al

in Journal of Dental Research (2002, December), 81(Sp. Iss. B), 239-239

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See detailEffects of 6-substituted 2-oxo-2H-1-benzopyran-3-carbowylic acide derivatives on cellular invasion in vitro
Kempen, I.; Frankenne, F.; Noël, Agnès ULg et al

Poster (2002, November 15)

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See detailMatrix metalloproteinase-9, but not tissue inhibitor of matrix metalloproteinase-1, increases in the sputum from allergic asthmatic patients after allergen challenge
Cataldo, Didier ULg; Bettiol, J.; Noël, Agnès ULg et al

in CHEST (2002), 122(5), 1553-1559

Objective: The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metallloproteinase (TIMP)-1 in the ... [more ▼]

Objective: The aim of the study was to determine whether allergen inhalation modulates the levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of matrix metallloproteinase (TIMP)-1 in the induced sputum recovered from patients during a late-phase reaction. Method: Eight allergic asthma patients and five healthy control subjects inhaled a dose of Dermatophagoides pteronyssinus extract corresponding to the provocative concentration of the allergen causing a 20% fall in FEV1 and saline solution. Lung function was carefully monitored for 6 h, and an induced sputum test was performed at 6 h after sham challenge or allergen challenge. The total and differential cell counts were analyzed, and the levels of MMP-9 (by enzyme-linked immunosorbent assay [ELISA] and zymography), TIMP-1 (by ELISA), and albumin (by rocket immunoelectrophoresis) were measured. Results: The sputum eosinophil counts (p < 0.01) and MMP-9 levels (p < 0.05) increased significantly in atopic asthma patients after undergoing the allergen challenge but did not in the control subjects. By contrast, TIMP-1 and albumin levels were not significantly increased in any group. MMP-9 levels, measured after the allergen challenge in asthmatic patients, were significantly correlated with FEV1 variations after allergen inhalation (r = 0.51; p < 0.05) and with the sputum neutrophil percentage (r = 0.71; p < 0.01). Conclusion: The levels of MMP-9, but not TIMP-1, increase after inhaled allergen challenge in the sputum of allergic asthmatic patients. This protease increase may lead to a transient imbalance between MMP-9 and TIMP-1 favoring proteolytic extracellular matrix degradation. [less ▲]

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See detailRole of endocrine status and cell type in adhesion of human endometrial cells to the peritoneum in nude mice
Beliard, Aude ULg; Noël, Agnès ULg; Goffin, Frédéric ULg et al

in Fertility and Sterility (2002), 78(5), 973-978

Objective: To investigate the role of different cellular types (epithelial and stromal endometrial cells and peritoneal cells) in the ectopic implantation of endometrium and to evaluate the importance of ... [more ▼]

Objective: To investigate the role of different cellular types (epithelial and stromal endometrial cells and peritoneal cells) in the ectopic implantation of endometrium and to evaluate the importance of endocrine environment on the adhesion of endometrial cells to the peritoneum. Design: Experimental prospective study. Setting: University hospital, department of cell biology. Animal(s): One hundred one nude mice. Intervention(s): Monolayer culture of human epithelial and stromal endometrial cells obtained from patients undergoing hysterectomy or laparoscopy for benign disease. Intraperitoneal injection of cells into nude mice. Main Outcome Measure(s): Two weeks after cell injection, adhesion of endometrial cells was evaluated by histological and immunohistochemical examination. Result(s): Mixed cultures of stromal and epithelial cells, but not purified epithelial or stromal cells alone, adhered to the mouse peritoneum and led to endometriotic-like nodules. Pretreatment of cells with estrogen alone or with estrogen and progestin resulted in a higher percentage of animals developing endometriotic-like nodules, whereas treatment with progestin alone did not affect endometriotic implantation. Conclusion(s): Our data indicate that the success of endometrial cell implantation is dependent on the cooperativeness between stromal and epithelial endometrial cells, as well as on the endocrine environment of endometrial cells, but not that of recipient animals. The results emphasize the role of both endometrial cell types for ectopic implantation. (C) 2002 by American Society for Reproductive Medicine. [less ▲]

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See detailMouse Aortic Ring Assay: A New Approach of the Molecular Genetics of Angiogenesis
Masson, Véronique ULg; Devy, L.; Grignet-Debrus, Christine ULg et al

in Biological Procedures Online (2002), 4

Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serine-proteases and matrix ... [more ▼]

Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serine-proteases and matrix metalloproteases in angiogenesis, we have adapted to the mouse, the aortic ring assay initially developed in the rat. The use of deficient mice allowed us to demonstrate that PAI-1 is essential for angiogenesis while the absence of an MMP, MMP-11, did not affect vessel sprouting. We report here that this model is attractive to elucidate the cellular and molecular mechanisms of angiogenesis, to identify, characterise or screen "pro- or anti-angiogenic agents that could be used for the treatment of angiogenesis-dependent diseases. Approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer. [less ▲]

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See detailMatrix metalloproteinase-9 contributes to choroidal neovascularization
Lambert, Vincent ULg; Munaut, Carine ULg; Jost, M. et al

in American Journal of Pathology (2002), 161(4), 1247-1253

Age-related macular degeneration (AMD) is the primary cause of irreversible photoreceptors loss in adult patients and current therapies are limited. Increased levels of matrix metalloproteinases (MMPs ... [more ▼]

Age-related macular degeneration (AMD) is the primary cause of irreversible photoreceptors loss in adult patients and current therapies are limited. Increased levels of matrix metalloproteinases (MMPs) have been documented in neovascularization of severe ocular pathologies such as AMD and proliferative diabetic retinopathy. We report here that MMP-9 (gelatinase B) expression is induced and temporally regulated in the course of experimental choroidal neovascularization. We used transgenic mice expressing beta-galactosidase reporter gene under the dependence of MMP-9 promoter and RT-PCR analysis on choroidal neovascular structures microdissected from serial sections by laser pressure catapulting to show that MMP-9 expression is up-regulated concomitantly with the appearance of inflammatory cells in the subretinal lesion. In mice deficient in MMP-9 expression the development of choroidal neovascularization induced by laser photocoagulation still occurred, but at a reduced level. [less ▲]

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See detailTumor cell and stromal cell interactions during breast cancer progression
Noël, Agnès ULg; Foidart, Jean-Michel ULg

in Journal of Molecular Medicine (2002, September)

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See detailHuman breast adenocarcinoma cell lines promote angiogenesis by providing cells with uPA-PAI-1 and by enhancing their expression
Bajou, Khalid ULg; Lewalle, J. M.; Martinez, C. R. et al

in International Journal of Cancer = Journal International du Cancer (2002), 100(5), 501-506

During angiogenesis, endothelial cells use uPA and PAI-I to migrate and degrade the basement membrane surrounding capillary blood vessels. Invasive tumor cells produce a large amount of uPA that could ... [more ▼]

During angiogenesis, endothelial cells use uPA and PAI-I to migrate and degrade the basement membrane surrounding capillary blood vessels. Invasive tumor cells produce a large amount of uPA that could bind uPAR present at the endothelial cell surface to facilitate their invasion. To verify this hypothesis, endothelial cells were incubated with conditioned medium (CM) from two breast cancer cell lines (MCF7 and MDA MB 231 cells). Within a short incubation period (30 min) with both CM, an increase of uPA, PAW and uPA-PAI-I complex was detected in endothelial cell layer as assessed by casein zymography, ELISA and uPA immunostaining. The extent of this enhancement was related to the levels of uPA secreted by tumor cells (high in MDA MB 231 cells and low in MCF7 cells). After 2 hr of incubation, the CM from both tumor cells upregulated uPA and PAI-I mRNA levels in endothelial cells in a time-dependent manner. The uPA increase in the cell layer could not be attributable to an increase of uPAR level. Only the CM from highly invasive MDA MB 231 cells increased the angiogenic morphotype of endothelial cells assessed in a collagen gel. A single addition of amino-terminal fragment of uPA (ATF) was able to abolish the angiogenic effect induced by MDA MB 231 cell CM. Our data demonstrate that the interactions occurring between breast tumor cells and endothelial cells can modulate tumor angiogenesis at least by two mechanisms: an increase of uPA and PAI-I cell surface-binding and of their expression by endothelial cells. (C) 2002 Wiley-Liss, Inc. [less ▲]

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