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

被引：86

作者：

Arulanandam, Rozanne ^{[1
]}

Batenchuk, Cory ^{[1
]}

Angarita, Fernando A. ^{[2
]}

Ottolino-Perry, Kathryn ^{[2
]}

Cousineau, Sophie ^{[1
]}

Mottashed, Amelia ^{[1
]}

Burgess, Emma ^{[1
]}

Falls, Theresa J. ^{[1
]}

De Silva, Naomi ^{[1
]}

Tsang, Jovian ^{[1
]}

Howe, Grant A. ^{[1
]}

Bourgeois-Daigneault, Marie-Claude ^{[1
]}

Conrad, David P. ^{[1
]}

Daneshmand, Manijeh ^{[1
]}

Breitbach, Caroline J. ^{[3
]}

Kim, David H. ^{[3
]}

Raptis, Leda ^{[6
]}

Sad, Subash ^{[7
]}

Atkins, Harold ^{[1
]}

Huh, Michael S. ^{[1
]}

Diallo, Jean-Simon ^{[1
]}

Lichty, Brian D. ^{[4
]}

Ilkow, Carolina S. ^{[1
]}

Le Boeuf, Fabrice ^{[1
]}

Addison, Christina L. ^{[1
]}

McCart, J. Andrea ^{[2
,5
]}

Bell, John C. ^{[1
]}

机构：

[1] Ottawa Hosp Res Inst, Ctr Innovat Canc Therapeut, Ottawa, ON K1H 8L6, Canada

[2] Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON M5G 2M9, Canada

[3] SillaJen Biotherapeut, San Francisco, CA 94111 USA

[4] McMaster Univ, McMaster Immunol Res Ctr, Hamilton, ON L8S 4K1, Canada

[5] Univ Toronto, Mt Sinai Hosp, Dept Surg, Toronto, ON M5G 1X5, Canada

[6] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada

[7] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada

来源：

CANCER CELL | 2015年 / 28卷 / 02期

基金：

加拿大自然科学与工程研究理事会;

关键词：

ENDOTHELIAL GROWTH-FACTOR; CELL CARCINOMA; ORF VIRUS; IN-VIVO; CANCER; STAT3; ANGIOGENESIS; VEGF; THERAPY; IDENTIFICATION;

D O I：

10.1016/j.ccell.2015.06.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. VEG/FNEGFR2 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.

引用

页码：210 / 224

页数：15

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