Anti‐cancer effect of targeting fibroblast activation protein alpha in glioblastoma through remodeling macrophage phenotype and suppressing tumor progression
Yazhou Miao, Yuxuan Deng, Jinqiu Liu, Jing Wang, Boyi Hu, Shuyu Hao, Herui Wang, Zhe Zhang, Zeping Jin, Yang Zhang, Chunzhao Li, Peng Zhang, Hong Wan, Shaodong Zhang, Jie Feng, Nan Ji
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.