| Literature DB >> 26212250 |
Rozanne Arulanandam1, Cory Batenchuk1, Fernando A Angarita2, Kathryn Ottolino-Perry2, Sophie Cousineau1, Amelia Mottashed1, Emma Burgess1, Theresa J Falls1, Naomi De Silva1, Jovian Tsang1, Grant A Howe1, Marie-Claude Bourgeois-Daigneault1, David P Conrad1, Manijeh Daneshmand1, Caroline J Breitbach3, David H Kirn3, Leda Raptis4, Subash Sad5, Harold Atkins1, Michael S Huh1, Jean-Simon Diallo1, Brian D Lichty6, Carolina S Ilkow1, Fabrice Le Boeuf1, Christina L Addison1, J Andrea McCart7, John C Bell8.
Abstract
Oncolytic viruses designed to attack malignant cells can in addition infect and destroy tumor vascular endothelial cells. We show here that this expanded tropism of oncolytic vaccinia virus to the endothelial compartment is a consequence of VEGF-mediated suppression of the intrinsic antiviral response. VEGF/VEGFR2 signaling through Erk1/2 and Stat3 leads to upregulation, nuclear localization, and activation of the transcription repressor PRD1-BF1/Blimp1. PRD1-BF1 does not contribute to the mitogenic effects of VEGF, but directly represses genes involved in type I interferon (IFN)-mediated antiviral signaling. In vivo suppression of VEGF signaling diminishes PRD1-BF1/Blimp1 expression in tumor vasculature and inhibits intravenously administered oncolytic vaccinia delivery to and consequent spread within the tumor.Entities:
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Year: 2015 PMID： 26212250 DOI： 10.1016/j.ccell.2015.06.009
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743