Suppression of HMGB1 Released in the Glioblastoma Tumor Microenvironment Reduces Tumoral Edema

Bangxing Hong, Kamaldeen Muili, Chelsea Bolyard, Luke Russell, Tae Jin Lee, Yeshavanth Banasavadi-Siddegowda, Ji Young Yoo, Yuanqing Yan, Leomar Y. Ballester, Kurt H. Bockhorst, Balveen Kaur*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

HMGB1 is a ubiquitously expressed intracellular protein that binds DNA and transcription factors and regulates chromosomal structure and function. Under conditions of cell death or stress, it is actively or passively released by cells into the extracellular environment, where it functions as damage-associated molecular pattern (DAMP) that orchestrates pro-inflammatory cytokine release and inflammation. Our results demonstrate that HMGB1 is secreted in the tumor microenvironment after oncolytic HSV (oHSV) infection in vitro and in vivo. The impact of secreted HMGB1 on tumor growth and response to oncolytic viral therapy was evaluated by using HMGB1-blocking antibodies in vitro and in mice bearing intracranial tumors. IVIS and MRI imaging was utilized to visualize in real time virus spread, tumor growth, and changes in edema in mice. Our data showed that HMGB1 released in tumor microenvironment orchestrated increased vascular leakiness and edema. Further HMGB1 blocking antibodies rescued vascular leakiness and enhanced survival of intracranial glioma-bearing mice treated with oHSV.

Original languageEnglish (US)
Pages (from-to)93-102
Number of pages10
JournalMolecular Therapy - Oncolytics
Volume12
DOIs
StatePublished - Mar 29 2019
Externally publishedYes

Keywords

  • blood brain barrier
  • brain tumor
  • brain tumor
  • cancer
  • CNS
  • HMGB1
  • HSV-1
  • oncolytic
  • vascular permeability

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

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