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

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Item Type:	Article
Title:	Anti-angiogenesis and anti-immunosuppression gene therapy through targeting COUP-TFII in an in situ glioblastoma mouse model
Creators Name:	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, C.A., Wang, X. and Du, J.
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.
Keywords:	Animal Disease Models, Brain Neoplasms, COUP Transcription Factor II, Genetic Therapy, Glioblastoma, Immunosuppression Therapy, Nanoparticles, Pathologic Neovascularization, Tumor Cell Line, Animals, Mice
Source:	Cancer Gene Therapy
ISSN:	0929-1903
Publisher:	Nature Publishing Group
Volume:	31
Number:	8
Page Range:	1135-1150
Date:	August 2024
Official Publication:	https://doi.org/10.1038/s41417-024-00799-z
PubMed:	View item in PubMed

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