Retinoids Induce t-PA Synthesis by C6 Glioma Cells -Role in Tumoral Haemorrhagic Necrosis

Pernod, Gilles; Amalfitano, G.; Magueresse, B. Le; Berger, François; Polack, Benoı̂t; Kolodié, L

doi:10.1055/s-0038-1650270

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…SDS-PAGE zymography was carried out as previously described [30], using 40 l of concentrated sample. After electrophoresis, the 10% polyacrylamide gel was washed in 2.5% Triton X-100 for 1 h, and rinsed in distilled water.…”

Section: Zymographic Analysismentioning

confidence: 99%

“…Molecular weight calibration was performed using known molecular weight standards run under the same conditions, together with human tPA and uPA. In the first series of experiments, we initially determined the PA specificity either by incorporating a polyclonal anti-tPA antibody (80 g/ml) into the fibrin layer or by adding amiloride (1 mM) to identify uPA [30].…”

Section: Zymographic Analysismentioning

confidence: 99%

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Plasminogen Activator Inhibitor-1 Is Expressed in Cultured Rat Sertoli Cells1

Magueresse-Battistoni

Pernod

Sigillo

et al. 1998

Biology of Reproduction

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Sertoli cells secrete plasminogen activators (PAs) on both sides of the blood-testis barrier, i.e., in the basal and apical compartments of the seminiferous tubules, whereas peritubular cells secrete plasminogen activator inhibitor-1 (PAI-1), a fast-acting and specific PA inhibitor. While it is likely that PAI-1 produced by peritubular cells counteracts the basal secretion of PA, the nature of the PA inhibitor acting in the apical compartment remains to be demonstrated. In the present study, we showed that Sertoli cells recovered from 20-day-old rats and cultured contained a transcript of 3-3.2 kilobases, which hybridized specifically to a PAI-1 cDNA probe (Northern blot). We verified that the observed PAI-1 transcript could not result solely from the peritubular cells (weakly contaminating the Sertoli cell cultures), by comparing PAI-1 mRNA levels of Sertoli and peritubular cells recovered from 20-day-old rats and cultured. We also demonstrated that cultured Sertoli cells secreted a protein that complexed with tissue-type PA (zymography), indicating that it was biologically active. This protein comigrated with purified PAI-1 as a doublet of 46 and 49 kDa (Western blot). The trophic hormone FSH decreased PAI-1 messenger RNA as well as immunoreactive PAI-1 protein (probably via the cAMP protein kinase A pathway), whereas transforming growth factor ss1 and basic fibroblast growth factor (in a nanomolar concentration) increased both of these. These observations support the hypothesis that PAI-1 is expressed by Sertoli cells and is under a complex hormonal (FSH) and paracrine and/or autocrine control exerted at least by basic fibroblast growth factor and transforming growth factor ss1.

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Section: Zymographic Analysismentioning

confidence: 99%

Section: Zymographic Analysismentioning

confidence: 99%

Plasminogen Activator Inhibitor-1 Is Expressed in Cultured Rat Sertoli Cells1

Magueresse-Battistoni

Pernod

Sigillo

et al. 1998

Biology of Reproduction

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“…17,18 Aside from its fibrinolytic activity, several reports suggest that tPA may also have antiangiogenic properties through and independently of angiostatin, especially when combined with FSDs. 2,8,10,12 Although systematically administered angiostatin has shown limited efficacy in clinical trials, activity might be increased if angiostatin was produced inside the tumor and was, in addition, associated with other antiangiogenic compounds.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 In this glioma model, we were interested in studying the antiangiogenic and/or antitumor potential of tPA in combination with an FSD. To evaluate this, we used a lentiviral vector to overexpress tPA in situ in C6 tumor cells, which were implanted into nude mice treated daily with the FSD, captopril.…”

Section: Introductionmentioning

confidence: 99%

Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model

et al. 2008

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Tissue-type plasminogen activator (tPA) plays a major role in the fibrinolytic system. According to several reports, tPA may also have antiangiogenic properties, especially in combination with a free sulfhydryl donor (FSD). In the rat C6 glioma model, in vitro and in vivo tPA synthesis by glioma cells is enhanced by differentiation therapy. To address the antiangiogenic potential of tPA in this model, tPA was overexpressed in glioma tumors by ex vivo transduction of C6 cells with a lentiviral vector encoding tPA. The transduced cells were subcutaneously implanted into nude mice. Gene transfer allowed for efficient synthesis of tPA by the C6 tumors. Although the treatment of tPA þ tumor-bearing animals with the FSD captopril generated angiostatin in situ and reduced endothelial vascularization of the tumors, it had no effect on tumor growth. Alternative mechanisms could account for this lack of effect and consequently have important implications for vascular the treatment of glioblastoma.

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“…First, the description of such a procoagulant pattern makes this cell line a complete model of cell‐dependent hemostasis. Indeed, a few years ago we described the ability of this cell line to promote fibrinolysis by synthesizing and expressing tissue‐type plasminogen activator (t‐PA) [2]. We also demonstrated that these cells were able to bind plasminogen and to enhance t‐PA‐induced cell‐bound plasminogen activation by inducing significant modifications in the kinetic parameters of the plasminogen‐t‐PA interaction [3].…”

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confidence: 99%