Multimutated Herpes Simplex Virus G207 Is a Potent Inhibitor of Angiogenesis

The mode of the antitumoral activity of multimutated oncolytic herpes simplex virus type 1 G207 has not been fully elucidated yet. Because the antitumoral activity of many drugs involves the inhibition of tumor blood vessel formation, we determined if G207 had an influence on angiogenesis. Monolayer...

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Bibliographic Details
Published in:Neoplasia (New York, N.Y.) N.Y.), 2004-11, Vol.6 (6), p.725-735
Main Authors: Cinatl, Jindrich, Michaelis, Martin, Drievert, Pablo Hernáiz, Cinatl, Jaroslav, Hrabeta, Jan, Suhan, Tatyana, Wilhelm Doerr, Hans, Vogel, Jens-Uwe
Format: Article
Language:English
Subjects:
Angiogenesis
Animals
Cell Line, Tumor
Cytopathogenic Effect, Viral
Electrophoresis, Polyacrylamide Gel
Endothelial Cells - virology
G207
HSV-1
human rhabdomyosarcoma
Humans
Immunoblotting
Immunohistochemistry
Microscopy, Electron, Transmission
Mutation
Neovascularization, Pathologic - virology
Reverse Transcriptase Polymerase Chain Reaction
Rhabdomyosarcoma - virology
ribonucleotide reductase
Simplexvirus - genetics
Simplexvirus - physiology
Umbilical Veins
Virus Replication - physiology
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Summary:The mode of the antitumoral activity of multimutated oncolytic herpes simplex virus type 1 G207 has not been fully elucidated yet. Because the antitumoral activity of many drugs involves the inhibition of tumor blood vessel formation, we determined if G207 had an influence on angiogenesis. Monolayers of human umbilical vein endothelial cells and human dermal microvascular endothelial cells, but not human dermal fibroblasts, bronchial epithelial cells, and retinal glial cells, were highly sensitive to the replicative and cytotoxic effects of G207. Moreover, G207 infection caused the destruction of endothelial cell tubes in vitro. In the in vivo Matrigel plug assay in mice, G207 suppressed the formation of perfused vessels. Intratumoral treatment of established human rhabdomyosarcoma xenografts with G207 led to the destruction of tumor vessels and tumor regression. Ultrastructural investigations revealed the presence of viral particles in both tumor and endothelial cells of G207-treated xenografts, but not in adjacent normal tissues. These findings show that G207 may suppress tumor growth, in part, due to inhibition of angiogenesis.
ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1593/neo.04265