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

Solly, F.
Simard, B.
Bolle, N.
Polack, B.
Published in Cancer gene therapy. 2008, vol. 15, no. 10, p. 685-692
Abstract 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+ 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.
Keywords Angiostatins/metabolismAngiotensin-Converting Enzyme Inhibitors/pharmacology/therapeutic useAnimalsAntigens, CD31/analysisBlotting, WesternCaptopril/pharmacology/therapeutic useCell Line, TumorCombined Modality TherapyGene Therapy/methodsGenetic Vectors/geneticsGlioma/drug therapy/pathology/therapyImmunohistochemistryLentivirus/geneticsMaleMiceMice, NudeNeovascularization, Pathologic/drug therapy/metabolism/therapyRatsTissue Plasminogen Activator/genetics/metabolism/physiologyTumor Burden/drug effectsXenograft Model Antitumor Assays
PMID: 18535615
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Research groups Endothélium vasculaire (11)
Recherche translationnelle : anomalies de l'hémostase et thromboses (504)
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SOLLY, F. et al. Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model. In: Cancer gene therapy, 2008, vol. 15, n° 10, p. 685-692. doi: 10.1038/cgt.2008.36 https://archive-ouverte.unige.ch/unige:2535

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Deposited on : 2009-08-28

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