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. 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.
Cinatl
Jindrich
J
Institute of Medical Virology, Center of Hygiene, Paul-Ehrlich Str. 40, Frankfurt am Main D-60596, Germany. Cinatl@em.uni-frankfurt.de
Michaelis
Martin
M
Driever
Pablo Hernáiz
PH
Cinatl
Jaroslav
J
Hrabeta
Jan
J
Suhan
Tatyana
T
Doerr
Hans Wilhelm
HW
Vogel
Jens-Uwe
JU
D000818:Animals; D045744:Cell Line, Tumor; D003588:Cytopathogenic Effect, Viral; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000821:virology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009389:Neovascularization, Pathologic / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000821:virology; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D014471:Umbilical Veins; D014779:Virus Replication / Q000502:physiology
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