Regulation of the uPAR/uPA system expressed on monocytes by the deactivating cytokines, IL‐4, IL‐10 and IL‐13: consequences on cell adhesion to vitronectin and fibrinogen

Paysant, Jérôme; Vasse, Marc; Lenormand, Bernard; Pourtau, Jérôme; Vannier, Jean‐Pierre; Soria, Claudine

doi:10.1046/j.1365-2141.1998.00528.x

Cited by 18 publications

(17 citation statements)

References 35 publications

(36 reference statements)

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“…(Mean ± SEM of 2 separate experiments.) on this cell line and this increased adhesivity was suppressed by preincubating the cells with a monoclonal antibody against u-PAR which blocks the interaction with vitronectin (Paysant et al, 1998). This is also supported by the fact that NaPa did not modify the cell adhesion either on vitronectin nor on u-PAR of MCF-7 and MCF-7 ras cells.…”

Section: Discussionsupporting

confidence: 56%

“…Flow cytometry analysis were performed on non-permeabilized cells, as previously described (Paysant et al, 1998). ICAM-1 (CD104), LFA-1 (CD11a) and MAC-1 (CD11b) expression on breast cancer cells were determined by direct immunofluorescence, while u-PA and PAI-1 were detected by indirect immunofluorescence.…”

Section: Flow Cytometry Analysismentioning

confidence: 99%

“…Adhesion assay was performed as previously described (Paysant et al, 1998), with minor modifications. Tissue culture plates (96 wells) were prepared as follows: 50 µl per well of vitronectin (0.5 µg ml Ϫ1 ) or fibronectin (100 µg ml Ϫ1 ) were incubated overnight at 4˚C.…”

Section: Adhesion Assaymentioning

confidence: 99%

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Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules

Vasse¹,

Thibout

Paysant³

et al. 2001

Br J Cancer

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Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionsupporting

confidence: 56%

Section: Flow Cytometry Analysismentioning

confidence: 99%

See 1 more Smart Citation

Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules

Vasse¹,

Thibout

Paysant³

et al. 2001

Br J Cancer

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“…A previously reported assay was used to measure UPAR-mediated adhesion of monocytes to vitronectin (20) under conditions outlined in the text and Fig. 4.…”

Section: Methodsmentioning

confidence: 99%

Cell adhesion regulates gene expression at translational checkpoints in human myeloid leukocytes

Mahoney

Weyrich

Dixon

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Engagement of adhesion molecules on monocytes and other myeloid leukocytes, which are effector cells of the innate immune system, not only tethers the leukocytes in place but also transmits outside-in signals that induce functional changes and alter gene expression. We found that a subset of mRNAs that are induced or amplified by adhesion of human monocytes to P-selectin via its surface ligand, P-selectin glycoprotein 1, have characteristics that suggest specialized translational control. One of these codes for urokinase plasminogen activator receptor (UPAR), a critical surface protease receptor and regulator of cell adhesion and migration. Although UPAR transcripts are induced by adhesion, rapid synthesis of the protein uses constitutive mRNA without a requirement for new transcription and is regulated by mammalian target of rapamycin, demonstrating new biologic roles for the signaldependent translation pathway controlled by this intracellular kinase. The synthesis of UPAR in monocytic cells is also regulated by eukaryotic translation initiation factor 4E, a second key translational checkpoint, and phosphorylation of eukaryotic translation initiation factor 4E is induced by adhesion of monocytes to Pselectin. Translationally controlled display of UPAR by monocytes confers recognition of the matrix protein, vitronectin. Adhesiondependent signaling from the plasma membrane to translational checkpoints represents a previously unrecognized mechanism for regulating surface phenotype that may be particularly important for myeloid leukocytes and other cells that are specialized for rapid inflammatory and vascular responses.

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“…93 Others report that IL-13 potently induces MMP-2, -9, -12, -13, and -14, and cathepsins B, L, S, H, and K. 97 100 SMCs, 101,102 and monocyte/macrophages. 103,104 With regard to extracellular matrix synthesis, IFN-␥ inhibits collagen production by SMCs, the principal source of collagen in the arterial wall. 105 In all these cases, the isolated cytokine effects are measured in vitro, whereas the integration of effects in a given cytokine milieu in vivo may be distinctively different.…”

Section: Pattern Of Cytokine Expression In Aortic Occlusive and Aneurmentioning

confidence: 99%

Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms

Shimizu

Mitchell

Libby

2006

ATVB

564

478

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Abstract-Expansion and rupture of abdominal aortic aneurysms (AAA) result in high morbidity and mortality rates. Like stenotic atherosclerotic lesions, AAA accumulate inflammatory cells, but usually exhibit much more extensive medial damage. Leukocyte recruitment and expression of pro-inflammatory Th1 cytokines typically characterize early atherogenesis of any kind, and modulation of inflammatory mediators mutes atheroma formation in mice. 1 However, the mechanistic differences between stenotic and aneurysmal manifestations of atherosclerosis remain unexplained. We recently showed that aortic allografts deficient in interferon-␥ (IFN-␥) signaling developed AAA correlating with skewed Th2 cytokine environments, suggesting important regulatory roles for Th1/Th2 cytokine balance in modulating matrix remodeling and important implications for the pathophysiology of aortic aneurysm and atherosclerosis. Key Words: aortic aneurysm Ⅲ atherosclerosis Ⅲ cytokine Ⅲ pathogenesis Ⅲ T-lymphocytes Ⅲ transplantation A ortic aneurysms are permanent and localized aortic dilations defined as having diameters 1.5-times greater than normal (ie, Ͼ3 cm diameter for abdominal aortic aneurysms [AAA]). In comparison, the term aortic ectasia describes localized aortic enlargement Ͻ1.5-times normal diameter. 2 Although most aneurysms remain asymptomatic and undiagnosed, risk of rupture increases dramatically when diameters exceed 5.5 cm. Despite surgical advances, the prognosis of ruptured AAA remains poor, and the overall mortality remains high (80% to 90%). 3 Although surgical or endovascular repair constitutes the major therapeutic options for AAA Ͼ5.5 cm, such invasive procedures provide no therapeutic advantage for AAA Ͻ5.5 cm diameter.Most AAA develop below the renal arteries and end above the bifurcation of the iliac arteries; they typically exhibit a fusiform morphology, with symmetrical circumferential enlargement involving all layers of the aortic wall. Less frequently, aneurysms have a saccular form, with aneurysmal degeneration affecting only part of the aortic circumference. The AAA wall usually becomes laminated with thrombus and its intraluminal diameter often appears relatively normal by angiography. Important histological features of aneurysms include chronic adventitial and medial inflammatory cell infiltration, elastin fragmentation and degeneration, and medial attenuation. Collagen (especially types I and III) in the media and adventitia provides tensile strength to the aortic wall. Collagen synthesis increases during the early stages of aneurysm formation, suggesting a repair process. 4 However, in later stages, collagen degradation exceeds its synthesis (accompanied by excessive degradation of other extracellular matrix macromolecules, notably elastin), ultimately favoring AAA rupture. Indeed, AAA exhibit increased local production of enzymes capable of degrading collagen and elastin extracellular matrix proteins. [5][6][7] In AAA, inflammatory cells (polymorphonuclear neutrophils, T cells, B cells, macrophages, mast c...

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Regulation of the uPAR/uPA system expressed on monocytes by the deactivating cytokines, IL‐4, IL‐10 and IL‐13: consequences on cell adhesion to vitronectin and fibrinogen

Cited by 18 publications

References 35 publications

Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules

Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules

Cell adhesion regulates gene expression at translational checkpoints in human myeloid leukocytes

Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms

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