Tissue-type plasminogen activator has antiangiogenic properties without effect on tumor growth in a rat C6 glioma model.
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.
Solly
F
F
DBPC, GREPI EA 2938, University Hospital of Grenoble, Grenoble, France.
Fish
R
R
Simard
B
B
Bolle
N
N
Kruithof
E
E
Polack
B
B
Pernod
G
G
D043168:Angiostatins / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D051381:Rats; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000806:Angiotensin-Converting Enzyme Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D043168:Angiostatins; D002216:Captopril; D010959:Tissue Plasminogen Activator