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Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model

Authors

  • F. Wang
  • S. Zhang
  • F. Sun
  • W. Chen
  • C. Liu
  • H. Dong
  • B. Cui
  • L. Li
  • C. Sun
  • W. Du
  • B. Liu
  • W. Fan
  • J. Deng
  • C.A. Schmitt
  • X. Wang
  • J. Du

Journal

  • Cancer Gene Therapy

Citation

  • Cancer Gene Ther 31 (8): 1135-1150

Abstract

  • Glioblastoma (GBM) is the most common and aggressive primary brain cancer; angiogenesis and immunosuppression exacerbate GBM progression. COUP-TFII demonstrates pro-angiogenesis activity; however, its role in glioma progression remains unclear. This study revealed that COUP-TFII promotes angiogenesis in gliomas by inducing transdifferentiation of glioma cells into endothelial-like cells. Mechanistic investigation suggested that COUP-TFII as a transcription factor exerts its function via binding to the promoter of TXNIP. Interestingly, COUP-TFII knockdown attenuated tumorigenesis and tumor progression in an immunocompetent mouse model but promoted tumor progression in an immuno-deficient mouse model. As an explanation, repression of COUP-TFII induces cellular senescence and activates immune surveillance in glioma cells in vitro and in vivo. In addition, we used heparin–polyethyleneimine (HPEI) nanoparticles to deliver COUP-TFII shRNA, which regulated tumor angiogenesis and immunosuppression in an in situ GBM mouse model. This study provides a novel strategy and potential therapeutic targets to treat GBM.


DOI

doi:10.1038/s41417-024-00799-z