Oncolytic HSV-Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition.

ABSTRACT:

Purpose

To examine the effect of oncolytic herpes simplex virus (oHSV) on NOTCH signaling in central nervous system tumors.

Experimental design

Bioluminescence imaging, reverse phase protein array proteomics, fluorescence microscopy, reporter assays, and molecular biology approaches were used to evaluate NOTCH signaling. Orthotopic glioma-mouse models were utilized to evaluate effects in vivo.

Results

We have identified that herpes simplex virus-1 (HSV-1; oncolytic and wild-type)-infected glioma cells induce NOTCH signaling, from inside of infected cells into adjacent tumor cells (inside out signaling). This was canonical NOTCH signaling, which resulted in activation of RBPJ-dependent transcriptional activity that could be rescued with dnMAML. High-throughput s

SUBMITTER: Otani Y 

PROVIDER: S-EPMC7325527 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature