1. Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model.
- Author
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Wang F, Zhang S, Sun F, Chen W, Liu C, Dong H, Cui B, Li L, Sun C, Du W, Liu B, Fan W, Deng J, Schmitt CA, Wang X, and Du J
- Subjects
- Animals, Mice, Humans, COUP Transcription Factor II genetics, COUP Transcription Factor II metabolism, Brain Neoplasms therapy, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms immunology, Cell Line, Tumor, Nanoparticles chemistry, Immunosuppression Therapy methods, Glioblastoma therapy, Glioblastoma genetics, Glioblastoma pathology, Glioblastoma immunology, Genetic Therapy methods, Disease Models, Animal, Neovascularization, Pathologic genetics, Neovascularization, Pathologic therapy
- 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., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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