References of "Noël, Agnès"
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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 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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See detailDevelopment of a Chitosan Nanofibrillar Scaffold for Skin Repair and Regeneration.
Tchemtchoua Tateu, Victor ULg; Atanasova, G.; Aqil, Abdelhafid ULg et al

in Biomacromolecules (2011), 12

The final goal of the present study was the development of a 3-D chitosan dressing that would shorten the healing time of skin wounds by stimulating migration, invasion, and proliferation of the relevant ... [more ▼]

The final goal of the present study was the development of a 3-D chitosan dressing that would shorten the healing time of skin wounds by stimulating migration, invasion, and proliferation of the relevant cutaneous resident cells. Three-dimensional chitosan nanofibrillar scaffolds produced by electrospinning were compared with evaporated films and freeze-dried sponges for their biological properties. The nanofibrillar structure strongly improved cell adhesion and proliferation in vitro. When implanted in mice, the nanofibrillar scaffold was colonized by mesenchymal cells and blood vessels. Accumulation of collagen fibrils was also observed. In contrast, sponges induced a foreign body granuloma. When used as a dressing covering full-thickness skin wounds in mice, chitosan nanofibrils induced a faster regeneration of both the epidermis and dermis compartments. Altogether our data illustrate the critical importance of the nanofibrillar structure of chitosan devices for their full biocompatibility and demonstrate the significant beneficial effect of chitosan as a wound-healing biomaterial. [less ▲]

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See detailLymphangiogenesis in post-natal tissue remodeling: Lymphatic endothelial cell connection with its environment.
Paupert, Jenny ULg; Sounni, Nor Eddine ULg; Noël, Agnès ULg

in Molecular Aspects of Medicine (2011), 32(2), 146-158

The main physiological function of the lymphatic vasculature is to maintain tissue fluid homeostasis. Lymphangiogenesis or de novo lymphatic formation is closely associated with tissue inflammation in ... [more ▼]

The main physiological function of the lymphatic vasculature is to maintain tissue fluid homeostasis. Lymphangiogenesis or de novo lymphatic formation is closely associated with tissue inflammation in adults (i.e. wound healing, allograft rejection, tumor metastasis). Until recently, research on lymphangiogenesis focused mainly on growth factor/growth factor-receptor pathways governing this process. One of the lymphatic vessel features is the incomplete or absence of basement membrane. This close association of endothelial cells with the underlying interstitial matrix suggests that cell-matrix interactions play an important role in lymphangiogenesis and lymphatic functions. However, the exploration of interaction between extracellular matrix (ECM) components and lymphatic endothelial cells is in its infancy. Herein, we describe ECM-cell and cell-cell interactions on lymphatic system function and their modification occurring in pathologies including cancer metastasis. [less ▲]

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See detailUnimpeded skin carcinogenesis in K14-HPV16 transgenic mice deficient for plasminogen activator inhibitor
Masset, Anne; Maillard, Catherine ULg; Sounni, Nor Eddine ULg et al

in International Journal of Cancer = Journal International du Cancer (2011), 128(2), 283-93

Angiogenesis, extracellular matrix remodeling and cell migration are associated with cancer progression and involve at least, the plasminogen activating system and its main physiological inhibitor, the ... [more ▼]

Angiogenesis, extracellular matrix remodeling and cell migration are associated with cancer progression and involve at least, the plasminogen activating system and its main physiological inhibitor, the plasminogen activator inhibitor-1 (PAI-1). Considering the recognized importance of PAI-1 in the regulation of tumor angiogenesis and invasion in murine models of skin tumor transplantation, we explored the functional significance of PAI-1 during early stages of neoplastic progression in the transgenic mouse model of multistage epithelial carcinogenesis (K14-HPV16 mice). We have studied the effect of genetic deletion of PAI-1 on inflammation, angiogenesis, lymphangiogenesis, as well as tumor progression. In this model, PAI-1 deficiency neither impaired keratinocyte hyperproliferation or tumor development, nor affected the infiltration of inflammatory cells and development of angiogenic or lymphangiogenic vasculature. We are reporting evidence for concomitant lymphangiogenic and angiogenic switches independent to PAI-1 status. Taken together, these data indicate that PAI-1 is not rate limiting for neoplastic progression and vascularization during premalignant progression, or that there is a functional redundancy between PAI-1 and other tumor regulators, masking the effect of PAI-1 deficiency in this long-term model of multi-stage epithelial carcinogenesis. [less ▲]

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See detailDentin Matrix Protein 1 induces membrane expression of VE-cadherin on endothelial cells and inhibits VEGF-induced angiogenesis by blocking VEGFR-2 phosphorylation.
Pirotte, Sophie ULg; Lamour, Virginie ULg; Lambert, Vincent ULg et al

in Blood (2011), 117(8), 2515-26

Dentin matrix protein 1 (DMP1) is a member of the Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) family, a group of proteins initially described as mineralized extracellular matrices ... [more ▼]

Dentin matrix protein 1 (DMP1) is a member of the Small Integrin-Binding LIgand N-linked Glycoproteins (SIBLINGs) family, a group of proteins initially described as mineralized extracellular matrices components. More recently, SIBLINGs have been implicated in several key steps of cancer progression, including angiogenesis. Although pro-angiogenic activities have been demonstrated for two SIBLINGs, the role of DMP1 in angiogenesis has not been addressed yet. We demonstrated that this extracellular matrix protein induced the expression of VE-cadherin, a key regulator of intercellular junctions and contact inhibition of growth of endothelial cells that is also known to modulate VEGFR-2 activity, the major high affinity receptor for VEGF. DMP1 induced VE-cadherin and p27(Kip1) expression followed by cell cycle arrest in human umbilical vein endothelial cells (HUVEC) in a CD44-dependent manner. VEGF-induced proliferation, migration and tubulogenesis responses were specifically blocked upon DMP1 pre-treatment of HUVEC. Indeed, subsequently to VE-cadherin induction, DMP1 inhibited VEGFR-2 phosphorylation and Src-mediated signaling. However, DMP1 did not interfere with bFGF-induced angiogenesis. In vivo, DMP1 significantly reduced laser-induced choroidal neovascularization lesions and tumor-associated angiogenesis. These data enable us to put DMP1 on the angiogenic chessboard for the first time and to identify this protein as a new specific inhibitor of VEGF-induced angiogenesis. [less ▲]

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See detailBone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization.
Lecomte, Julie ULg; Louis, Krystel; Detry, Benoît ULg et al

in Cellular and Molecular Life Sciences : CMLS (2011), 68

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a ... [more ▼]

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ( -/- ) mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV. [less ▲]

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See detailThe Angiostatic Protein 16K Human Prolactin Significantly Prevents Tumor-Induced Lymphangiogenesis by Affecting Lymphatic Endothelial Cells.
Kinet, Virginie; Castermans, K; Herkenne, Stéphanie ULg et al

in Endocrinology (2011)

The 16-kDa angiostatic N-terminal fragment of human prolactin (16K hPRL) has been reported to be a new potent anticancer compound. This protein has already proven its efficiency in several mouse tumor ... [more ▼]

The 16-kDa angiostatic N-terminal fragment of human prolactin (16K hPRL) has been reported to be a new potent anticancer compound. This protein has already proven its efficiency in several mouse tumor models in which it prevented tumor-induced angiogenesis and delayed tumor growth. In addition to angiogenesis, tumors also stimulate the formation of lymphatic vessels, which contribute to tumor cell dissemination and metastasis. However, the role of 16K hPRL in tumor-induced lymphangiogenesis has never been investigated. We establish in vitro that 16K hPRL induces apoptosis and inhibits proliferation, migration, and tube formation of human dermal lymphatic microvascular endothelial cells. In addition, in a B16F10 melanoma mouse model, we found a decreased number of lymphatic vessels in the primary tumor and in the sentinel lymph nodes after 16K hPRL treatment. This decrease is accompanied by a significant diminished expression of lymphangiogenic markers in primary tumors and sentinel lymph nodes as determined by quantitative RT-PCR. These results suggest, for the first time, that 16K hPRL is a lymphangiostatic as well as an angiostatic agent with antitumor properties. [less ▲]

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See detailCellules Tumorales Circulantes : détection, caractérisation et intérêts cliniques
Gilles, Christine ULg; COLLIGNON, Joëlle ULg; Noël, Agnès ULg et al

in Revue Médicale de Liège (2011), 66(5-6), 279-84

The metastatic process generates circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in bone marrow and other organs which can remain as occult metastases. Various methods and systems have ... [more ▼]

The metastatic process generates circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) in bone marrow and other organs which can remain as occult metastases. Various methods and systems have been developed to allow the isolation and identification of those cells but major technical limitations still exist. Research on CTCs is a nevertheless tremendously growing field of cancer research because of their potential clinical applications. CTCs indeed convey predictive information for the development of metastasis and recurrence, and prognostic information regarding patient survival. CTCs enumeration could also be used to monitor the effectiveness of adjuvant treatments. Moreover, enhancing our basic understanding of the metastatic process, CTCs, and DTCs in particular, are thought to contain subpopulations of cells with stem cells properties that would be responsible for relapses. [less ▲]

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See detailBiological aspects of angiogenesis in multiple myeloma.
Otjacques, Eléonore ULg; Binsfeld, Marilène ULg; Noël, Agnès ULg et al

in International Journal of Hematology (2011), 94(6), 505-18

Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant expansion of malignant plasma cells within the bone marrow (BM). One of the hallmarks of this disease is the close ... [more ▼]

Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant expansion of malignant plasma cells within the bone marrow (BM). One of the hallmarks of this disease is the close interaction between myeloma cells and neighboring cells within the BM. Angiogenesis, through the activation of endothelial cells, plays an essential role in MM biology. In the current review, we describe the angiogenesis process in MM by identifying the interacting cells, the pro- and anti-angiogenic cytokines modulated, and the extracellular matrix degrading proteases liable to participate in the pathophysiology. Finally, we highlight the impact of hypoxia (through hypoxia-inducible factor-1) and constitutive activation of nuclear factor-κB in this tumor-induced neo-vascularization. [less ▲]

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See detailCell cholesterol modulates metalloproteinase-dependent shedding of low-density lipoprotein receptor-related protein-1 (LRP-1) and clearance function.
Selvais, C.; D'Auria, L.; Tyteca, D. et al

in FASEB Journal (2011), 25(8), 2770-2781

Low-density lipoprotein receptor-related protein-1 (LRP-1) is a plasma membrane scavenger and signaling receptor, composed of a large ligand-binding subunit (515-kDa α-chain) linked to a shorter ... [more ▼]

Low-density lipoprotein receptor-related protein-1 (LRP-1) is a plasma membrane scavenger and signaling receptor, composed of a large ligand-binding subunit (515-kDa α-chain) linked to a shorter transmembrane subunit (85-kDa β-chain). LRP-1 cell-surface level and function are controlled by proteolytic shedding of its ectodomain. Here, we identified ectodomain sheddases in human HT1080 cells and demonstrated regulation of the cleavage by cholesterol by comparing the classical fibroblastoid type with a spontaneous epithelioid variant, enriched ∼2-fold in cholesterol. Two membrane-associated metalloproteinases were involved in LRP-1 shedding: a disintegrin and metalloproteinase-12 (ADAM-12) and membrane-type 1 matrix metalloproteinase (MT1-MMP). Although both variants expressed similar levels of LRP-1, ADAM-12, MT1-MMP, and specific tissue inhibitor of metalloproteinases-2 (TIMP-2), LRP-1 shedding from epithelioid cells was ∼4-fold lower than from fibroblastoid cells. Release of the ectodomain was triggered by cholesterol depletion in epithelioid cells and impaired by cholesterol overload in fibroblastoid cells. Modulation of LRP-1 shedding on clearance was reflected by accumulation of gelatinases (MMP-2 and MMP-9) in the medium. We conclude that cholesterol exerts an important control on LRP-1 levels and function at the plasma membrane by modulating shedding of its ectodomain, and therefore represents a novel regulator of extracellular proteolytic activities.-Selvais, C., D'Auria, L., Tyteca, D., Perrot, G, Lemoine, P., Troeberg, L., Dedieu, S., Noël, A., Nagase, H., Henriet, P., Courtoy, P. J., Marbaix, E., Emonard, H. Cell cholesterol modulates metalloproteinase-dependent shedding of low-density lipoprotein receptor-related protein-1 (LRP-1) and clearance function. [less ▲]

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