Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61

Kazuhiko Kurozumi, Jayson Hardcastle, Roopa Thakur, Joshua Shroll, Michal Nowicki, Akihiro Otsuki, E. Antonio Chiocca, Balveen Kaur

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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).

Original languageEnglish
Pages (from-to)1382-1391
Number of pages10
JournalMolecular Therapy
Volume16
Issue number8
DOIs
Publication statusPublished - Aug 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology

Cite this

Kurozumi, K., Hardcastle, J., Thakur, R., Shroll, J., Nowicki, M., Otsuki, A., Chiocca, E. A., & Kaur, B. (2008). Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61. Molecular Therapy, 16(8), 1382-1391. https://doi.org/10.1038/mt.2008.112