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PMID: 18545226 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular therapy : the journal of the American Society of Gene Therapy ·Vol. 16 ·No. 8 ·2008-08-00 ·Pages 1382-91

Kurozumi K, Hardcastle J, Thakur R, Shroll J, Nowicki M, Otsuki A, Chiocca EA, Kaur B

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).

MeSH Terms
Animals Blotting, Western Cell Line, Tumor Cysteine-Rich Protein 61/genetics,metabolism Glioma/pathology,therapy,virology Herpesvirus 1, Human/genetics,physiology Humans Mice Mice, Nude Neovascularization, Physiologic/genetics,physiology Oncolytic Virotherapy/methods RNA, Messenger/genetics,metabolism Rats Rats, Inbred F344 Reverse Transcriptase Polymerase Chain Reaction Up-Regulation Xenograft Model Antitumor Assays/methods
Chemicals
CCN1 protein, human CCN1 protein, rat Cysteine-Rich Protein 61 RNA, Messenger
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kurozumi Kazuhiko
Dardinger Laboratory for Neuro-oncology and Neurosciences, Department of Neurological Surgery, James Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, Ohio, USA.
Hardcastle Jayson
Thakur Roopa
Shroll Joshua
Nowicki Michal
Otsuki Akihiro
Chiocca E Antonio
Kaur Balveen
References (48)
48 references, click to expand
  1. Development of a rapid method to generate multiple oncolytic HSV vectors and their in vivo evaluation using syngeneic mouse tumor models.
    Gene Ther. 2006 Apr;13(8):705-14 PMID: 16421599
  2. Oncolytic herpes simplex virus vectors for cancer virotherapy.
    Cancer Gene Ther. 2002 Dec;9(12):967-78 PMID: 12522436
  3. Identification of human brain tumour initiating cells.
    Nature. 2004 Nov 18;432(7015):396-401 PMID: 15549107
  4. A rapid and simple cannulation technique for repeated sampling of cerebrospinal fluid in freely moving rats.
    Brain Res Bull. 1979 Jul-Aug;4(4):575-7 PMID: 487211
  5. Oncolytic herpes simplex virus type 1 and host immune responses.
    Curr Cancer Drug Targets. 2007 Mar;7(2):149-55 PMID: 17346106
  6. Adhesion of human umbilical vein endothelial cells to the immediate-early gene product Cyr61 is mediated through integrin alphavbeta3.
    J Biol Chem. 1998 Jan 30;273(5):3090-6 PMID: 9446626
  7. Endogenous inhibitors of angiogenesis in malignant gliomas: nature's antiangiogenic therapy.
    Neuro Oncol. 2005 Apr;7(2):106-21 PMID: 15831230
  8. Vasculostatin, a proteolytic fragment of brain angiogenesis inhibitor 1, is an antiangiogenic and antitumorigenic factor.
    Oncogene. 2005 May 19;24(22):3632-42 PMID: 15782143
  9. Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion.
    Mol Cell Biol. 1996 Apr;16(4):1326-34 PMID: 8657105
  10. Brain angiogenesis inhibitor 1 is differentially expressed in normal brain and glioblastoma independently of p53 expression.
    Am J Pathol. 2003 Jan;162(1):19-27 PMID: 12507886
  11. Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors.
    Cancer Res. 2007 Apr 15;67(8):3560-4 PMID: 17440065
  12. Treatment of malignant gliomas using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex viral mutant.
    Cancer Res. 1994 Aug 1;54(15):3963-6 PMID: 8033122
  13. Angiogenesis and its role in the behavior of astrocytic brain tumors.
    Front Biosci. 2004 Sep 01;9:3105-23 PMID: 15353341
  14. Cyr61 is overexpressed in gliomas and involved in integrin-linked kinase-mediated Akt and beta-catenin-TCF/Lef signaling pathways.
    Cancer Res. 2004 Mar 15;64(6):1987-96 PMID: 15026334
  15. Effect of adenovirus-mediated heat shock protein expression and oncolysis in combination with low-dose cyclophosphamide treatment on antitumor immune responses.
    Cancer Res. 2006 Jan 15;66(2):960-9 PMID: 16424031
  16. Innate immunity and angiogenesis.
    Circ Res. 2005 Jan 7;96(1):15-26 PMID: 15637304
  17. Identification of specific cellular genes up-regulated late in adenovirus type 12 infection.
    J Virol. 2005 Feb;79(4):2404-12 PMID: 15681441
  18. Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses.
    Nat Med. 1999 Aug;5(8):881-7 PMID: 10426310
  19. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.
    Cancer Cell. 2006 May;9(5):391-403 PMID: 16697959
  20. Contribution of vascular endothelial growth factor in the neovascularization process during the pathogenesis of herpetic stromal keratitis.
    J Virol. 2001 Oct;75(20):9828-35 PMID: 11559816
  21. Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis.
    Neuro Oncol. 2005 Oct;7(4):436-51 PMID: 16212809
  22. Suppression of thrombospondin 1 and 2 production by herpes simplex virus 1 infection in cultured keratocytes.
    Mol Vis. 2005 Mar 02;11:163-8 PMID: 15761388
  23. Genetic and biologic progression in astrocytomas and their relation to angiogenic dysregulation.
    Adv Anat Pathol. 2002 Jan;9(1):24-36 PMID: 11756757
  24. Oncolytic virotherapy for cancer treatment: challenges and solutions.
    J Gene Med. 2005 Nov;7(11):1380-9 PMID: 16025557
  25. Oncolytic HSV exerts direct antiangiogenic activity in ovarian carcinoma.
    Hum Gene Ther. 2005 Jun;16(6):765-78 PMID: 15960607
  26. Proteolysis of CCN1 by plasmin: functional implications.
    Cancer Res. 2005 Nov 1;65(21):9705-11 PMID: 16266990
  27. Preclinical pharmacology and toxicology of intravenous MV-NIS, an oncolytic measles virus administered with or without cyclophosphamide.
    Clin Pharmacol Ther. 2007 Dec;82(6):700-10 PMID: 17971816
  28. CYR61, a product of a growth factor-inducible immediate early gene, promotes angiogenesis and tumor growth.
    Proc Natl Acad Sci U S A. 1998 May 26;95(11):6355-60 PMID: 9600969
  29. Proteases and glioma angiogenesis.
    Brain Pathol. 2005 Oct;15(4):327-41 PMID: 16389945
  30. Multimutated herpes simplex virus g207 is a potent inhibitor of angiogenesis.
    Neoplasia. 2004 Nov-Dec;6(6):725-35 PMID: 15720798
  31. All in the CCN family: essential matricellular signaling modulators emerge from the bunker.
    J Cell Sci. 2006 Dec 1;119(Pt 23):4803-10 PMID: 17130294
  32. Angiogenic response caused by oncolytic herpes simplex virus-induced reduced thrombospondin expression can be prevented by specific viral mutations or by administering a thrombospondin-derived peptide.
    Cancer Res. 2007 Jan 15;67(2):440-4 PMID: 17234749
  33. Inflammation, inflammatory cells and angiogenesis: decisions and indecisions.
    Cancer Metastasis Rev. 2008 Mar;27(1):31-40 PMID: 18087678
  34. Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion.
    Lab Invest. 2006 Dec;86(12):1221-32 PMID: 17075581
  35. Insulin-like growth factor binding protein 2 promotes glioma development and progression.
    Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11736-41 PMID: 17606927
  36. Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas.
    Clin Cancer Res. 2004 Mar 15;10(6):2072-81 PMID: 15041728
  37. Role of matrix metalloproteinase-9 in angiogenesis caused by ocular infection with herpes simplex virus.
    J Clin Invest. 2002 Oct;110(8):1105-11 PMID: 12393846
  38. An oncolytic HSV-1 mutant expressing ICP34.5 under control of a nestin promoter increases survival of animals even when symptomatic from a brain tumor.
    Cancer Res. 2005 Apr 1;65(7):2832-9 PMID: 15805284
  39. Herpes simplex virus type 1-induced ribonucleotide reductase activity is dispensable for virus growth and DNA synthesis: isolation and characterization of an ICP6 lacZ insertion mutant.
    J Virol. 1988 Jan;62(1):196-205 PMID: 2824847
  40. Roles of sphingosine-1-phosphate (S1P) receptors in malignant behavior of glioma cells. Differential effects of S1P2 on cell migration and invasiveness.
    Exp Cell Res. 2007 May 1;313(8):1615-27 PMID: 17376432
  41. Coxsackievirus B3 infection induces cyr61 activation via JNK to mediate cell death.
    J Virol. 2004 Dec;78(24):13479-88 PMID: 15564459
  42. Angiopoietin: a TIE(d) balance in tumor angiogenesis.
    Mol Cancer Res. 2007 Jul;5(7):655-65 PMID: 17634421
  43. Effect of tumor microenvironment modulation on the efficacy of oncolytic virus therapy.
    J Natl Cancer Inst. 2007 Dec 5;99(23):1768-81 PMID: 18042934
  44. Oncolytic viruses driven by tumor-specific promoters.
    Curr Cancer Drug Targets. 2007 Mar;7(2):181-9 PMID: 17346110
  45. Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses.
    Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12873-8 PMID: 16908838
  46. Oncolytic HSV and erlotinib inhibit tumor growth and angiogenesis in a novel malignant peripheral nerve sheath tumor xenograft model.
    Mol Ther. 2007 Feb;15(2):279-86 PMID: 17235305
  47. Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF.
    Science. 1999 Jun 18;284(5422):1994-8 PMID: 10373119
  48. Effect of chemotherapy-induced DNA repair on oncolytic herpes simplex viral replication.
    J Natl Cancer Inst. 2006 Jan 4;98(1):38-50 PMID: 16391370
Article Info
Journal
Molecular therapy : the journal of the American Society of Gene Therapy
Abbr.
Mol Ther
ISSN
1525-0024
DOI
10.1038/mt.2008.112
Published
2008-08-00
Epub
2008-00-10
Pages
1382-91
Language
English
Region
United States
NLM ID
100890581
PMCID
PMC2659780
Subset
IM
Grants
NCI NIH HHS · P01 CA069246-110004 · United States
NINDS NIH HHS · 1K01NS059575 · United States
NINDS NIH HHS · K01 NS059575 · United States
NINDS NIH HHS · R21 NS056203-01A2 · United States
NINDS NIH HHS · R01 NS064607 · United States
NINDS NIH HHS · K01 NS059575-01A1 · United States
NCI NIH HHS · P01 CA069246 · United States
NINDS NIH HHS · R21 NS056203 · United States
NINDS NIH HHS · R01NS064607 · United States
NINDS NIH HHS · R01 NS064607-01 · United States
External Links
PubMed source DOI: 10.1038/mt.2008.112 PMC Full Text View journal details
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