Anti-cancer effect of targeting fibroblast activation protein alpha in glioblastoma through remodeling macrophage phenotype and suppressing tumor progression

  • CNS Neurosci Ther. 2022 Nov 15. doi: 10.1111/cns.14024.
Yazhou Miao  1  2 ,  Yuxuan Deng  1  2 ,  Jinqiu Liu  3 ,  Jing Wang  3 ,  Boyi Hu  3 ,  Shuyu Hao  1  2 ,  Herui Wang  4 ,  Zhe Zhang  1  2 ,  Zeping Jin  1  2 ,  Yang Zhang  1  2 ,  Chunzhao Li  1  2 ,  Peng Zhang  1  2 ,  Hong Wan  3 ,  Shaodong Zhang  3 ,  Jie Feng  3  5 ,  Nan Ji  1  2  6
Affiliations
  • 1. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
  • 2. National Clinical Research Center for Neurological Diseases (China), Beijing, China.
  • 3. Beijing Neurosurgical Institute, Capital Medical University, Fengtai, Beijing, China.
  • 4. Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 5. Beijing Cancer Institute, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
  • 6. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, China.
PMID: 36382346 DOI: 10.1111/cns.14024
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.

Keywords
PT100; epithelial-mesenchymal transition; fibroblast activation protein alpha; glioblastoma.
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