Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61.
Mol Ther
; 16(8): 1382-91, 2008 Aug.
Article
en En
| MEDLINE
| ID: mdl-18545226
ABSTRACT
Oncolytic viral therapy is under evaluation for toxicity and efficacy in clinical trials relating to several different tumors. We report a significant increase in the angiogenic index of oncolytic virus (OV)-treated glioma-matrigel implants (2.83-fold, P < 0.02). In a rat intracranial glioma model, large tumors from OV-treated animals were significantly more angiogenic than the phosphate-buffered saline (PBS)-treated control tumors (OV 101 +/- 21.6; PBS 19.8 +/- 10; P = 0.0037). Transcript profiling of OV-treated tumors revealed dysregulation of several transcripts involved in glioma angiogenesis. OV-mediated induction of CYR61 gene expression (8.94-fold, P = 0.001) correlated significantly with the presence of OV in tumor tissue in vivo (R = 0.7, P < 0.001). Further, induction of CYR61 mRNA and protein were confirmed in multiple human cancer cell lines and primary human tumor-derived cells in vitro, and in tumor lysate and cerebrospinal fluid (CSF) in vivo. Finally, we show that treatment of glioma cells with Cilengitide, known to counter CYR61-induced integrin activation, significantly suppressed the proangiogenic effect of OV treatment of gliomas (P < 0.05).
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Herpesvirus Humano 1
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Neovascularización Fisiológica
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Viroterapia Oncolítica
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Proteína 61 Rica en Cisteína
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Glioma
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos