VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor Vasculature to Oncolytic Virus Infection.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Arulanandam R,Batenchuk C,Angarita FA,Ottolino-Perry K,Cousineau S,Mottashed A,Burgess E,Falls TJ,De Silva N,Tsang J,Howe GA,Bourgeois-Daigneault MC,Conrad DP,Daneshmand M,Breitbach CJ,Kirn DH,Raptis L,Sad S,Atkins H

doi

10.1016/j.ccell.2015.06.009

subject

Has Abstract

pub_date

2015-08-10 00:00:00

pages

210-24

issue

2

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(15)00219-6

journal_volume

28

pub_type

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