2. Academic Validation
  3. Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model

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

  • Cancer Gene Ther. 2024 Jun 26. doi: 10.1038/s41417-024-00799-z.
Fei Wang # 1 2,  Shuo Zhang # 1 3,  Fengjiao Sun # 1,  Weiwei Chen # 1,  Cuilan Liu 1,  Hongliang Dong 1,  Bingjie Cui 1,  Lingyu Li 1,  Chunlong Sun 4,  Wen Du 4,  Bin Liu 1,  Wanfeng Fan 1,  Jiong Deng 1,  Clemens A Schmitt 5 6 7 8 9,  Xiuwen Wang 10,  Jing Du 11 12
Affiliations

Affiliations

  • 1 Medical Research Center, Binzhou Medical University Hospital, 256600, Binzhou, PR China.
  • 2 Medical Integration and Practice Center, Qilu Hospital of Shandong University, Shandong University, 250100, Jinan, PR China.
  • 3 Department of Gynecology, Binzhou Medical University Hospital, 256600, Binzhou, PR China.
  • 4 College of Biological and Environmental Engineering, Shandong University of Aeronautics, 256600, Binzhou, PR China.
  • 5 Johannes Kepler University, Altenbergerstraße 69, 4040, Linz, Austria.
  • 6 Department of Hematology and Oncology, Kepler University Hospital, Krankenhausstraße 9, 4020, Linz, Austria.
  • 7 Medical Department of Hematology, Oncology and Tumor Immunology, and Molekulares Krebsforschungszentrum - MKFZ, Campus Virchow Klinikum, Charité-Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353, Berlin, Germany.
  • 8 Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany.
  • 9 Deutsches Konsortium für Translationale Krebsforschung (German Cancer Consortium), Partner Site, Berlin, Germany.
  • 10 Medical Integration and Practice Center, Qilu Hospital of Shandong University, Shandong University, 250100, Jinan, PR China. wangxiuwen@csco.org.cn.
  • 11 Medical Research Center, Binzhou Medical University Hospital, 256600, Binzhou, PR China. djedith@bzmc.edu.cn.
  • 12 Department of Gynecology, Binzhou Medical University Hospital, 256600, Binzhou, PR China. djedith@bzmc.edu.cn.
  • # Contributed equally.
PMID: 38926596 DOI: 10.1038/s41417-024-00799-z
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.

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