Anti‐cancer effect of targeting fibroblast activation protein alpha in glioblastoma through remodeling macrophage phenotype and suppressing tumor progression. (15th November 2022)

• Record Type: Journal Article
• Authors: Miao, Yazhou; Deng, Yuxuan; Liu, Jinqiu; Wang, Jing; Hu, Boyi; Hao, Shuyu; Wang, Herui; Zhang, Zhe; Jin, Zeping; Zhang, Yang; Li, Chunzhao; Zhang, Peng; Wan, Hong; Zhang, Shaodong; Feng, Jie; Ji, Nan
• Is Part Of: CNS neuroscience & therapeutics. Volume 29:Number 3(2023)
• Page Start: 878
• Page End: 892
• Publication Date: 2022-11-15
• Subjects: epithelial–mesenchymal transition -- fibroblast activation protein alpha -- glioblastoma -- PT100; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.14024
• Languages: English
• ISSNs: 1755-5930

Abstract

Abstract: Introduction: Glioblastoma (GBM) is the most malignant form of glioma and has a poor median survival time. Fibroblast activation protein alpha (FAP) is a dual‐specificity serine protease that is strongly associated with the development and progression of human carcinomas. However, relatively little is known about the function of FAP and its potential as a therapeutic target in GBMs. Aims: In this study, we aimed to explore the role of FAP in GBM through a series of experiments and to evaluate the therapeutic effect of PT100, a small molecule inhibitor of FAP, on GBM. Results: Increased FAP expression was associated with poor survival in glioma. In vitro, FAP knockdown inhibited the process of EMT and caused a decrease in the number of M2 macrophages. In vivo, PT100 was confirmed to suppress the progression of GBMs significantly. Conclusions: FAP could serve as a biomarker and novel therapeutic target for the treatment of GBM and that PT100 is a promising drug for the treatment of GBM. Abstract : Fibroblast activation protein alpha (FAP) promotes the progression of glioblastoma by remodeling the morphology of tumor cells and the phenotype of macrophages. PT100, a small molecule inhibitor of FAP, is a promising drug for glioblastoma.