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

doi:10.1038/mt.2008.112

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

Research output: Contribution to journal › Article › peer-review

69 Scopus citations

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 language	English
Pages (from-to)	1382-1391
Number of pages	10
Journal	Molecular Therapy
Volume	16
Issue number	8
DOIs	https://doi.org/10.1038/mt.2008.112
State	Published - Aug 2008

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@article{898c83c6f2384cdd9b55cae320f089e9,

title = "Oncolytic HSV-1 infection of tumors induces angiogenesis and upregulates CYR61",

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).",

author = "Kazuhiko Kurozumi and Jayson Hardcastle and Roopa Thakur and Joshua Shroll and Michal Nowicki and Akihiro Otsuki and Chiocca, \{E. Antonio\} and Balveen Kaur",

note = "Funding Information: This work was supported by funding from the National Institutes of Health Grant (1K01NS059575 to B.K.; R01NS064607 to B.K.; P01 CA069246 to E.A.C.); The OSUCCC, Viral Oncogenesis Program seed grant (to B.K.); American Association for Neurological Surgeons/ Congress of Neurological Surgeons, Section on Tumors/BrainLAB International Research Fellowship (to K.K.); American Brain tumor Association Medical student fellowship (to J.S.); The Deans undergraduate research fund (to R.T.).",

year = "2008",

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AU - Kurozumi, Kazuhiko

AU - Hardcastle, Jayson

AU - Thakur, Roopa

AU - Shroll, Joshua

AU - Nowicki, Michal

AU - Otsuki, Akihiro

AU - Chiocca, E. Antonio

AU - Kaur, Balveen

N1 - Funding Information: This work was supported by funding from the National Institutes of Health Grant (1K01NS059575 to B.K.; R01NS064607 to B.K.; P01 CA069246 to E.A.C.); The OSUCCC, Viral Oncogenesis Program seed grant (to B.K.); American Association for Neurological Surgeons/ Congress of Neurological Surgeons, Section on Tumors/BrainLAB International Research Fellowship (to K.K.); American Brain tumor Association Medical student fellowship (to J.S.); The Deans undergraduate research fund (to R.T.).

PY - 2008/8

Y1 - 2008/8

N2 - 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).

AB - 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).

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DO - 10.1038/mt.2008.112

M3 - Article

C2 - 18545226

AN - SCOPUS:48349119172

SN - 1525-0016

VL - 16

SP - 1382

EP - 1391

JO - Molecular Therapy

JF - Molecular Therapy

IS - 8

ER -

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

Abstract

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