Ptprz1, also known as protein tyrosine phosphatase receptor type Z, is involved in multiple biological processes. It functions in cell proliferation, adhesion, and migration, and is associated with pathways such as survival signaling. It has been implicated in various diseases, especially glioma [4].

In glioblastoma (GBM), Ptprz1 is a key component in the PTN-Ptprz1 paracrine signaling. Tumour-associated macrophages secrete pleiotrophin (PTN) which binds to Ptprz1 on glioma stem cells, promoting GBM malignant growth. Disrupting Ptprz1 abrogates glioma stem cell maintenance and tumorigenic potential, and blocking this signaling axis suppresses GBM tumour growth [1]. RNA CAR T cells targeting Ptprz1 show antigen-specific and bystander antitumor activity in GBM, validating Ptprz1 as a GBM target [2]. Additionally, Ptprz1-MET fusion is associated with glioma progression from low-grade to high-grade glioma, and the MET inhibitor vebreltinib is being trialed for sGBM/IDH mutant glioblastoma patients with this fusion [3].

In conclusion, Ptprz1 plays a significant role in glioma development and progression, especially through its involvement in the PTN-Ptprz1 signaling axis and its fusion with MET. Research on Ptprz1, including through gene knockout or knockdown in relevant models, provides insights into glioma pathogenesis and potential therapeutic targets for glioma treatment.

References:

1. Shi, Yu, Ping, Yi-Fang, Zhou, Wenchao, Bao, Shideng, Bian, Xiu-Wu. 2017. Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth. In Nature communications, 8, 15080. doi:10.1038/ncomms15080. https://pubmed.ncbi.nlm.nih.gov/28569747/

2. Martinez Bedoya, Darel, Marinari, Eliana, Davanture, Suzel, Dutoit, Valérie, Migliorini, Denis. . PTPRZ1-Targeting RNA CAR T Cells Exert Antigen-Specific and Bystander Antitumor Activity in Glioblastoma. In Cancer immunology research, 12, 1718-1735. doi:10.1158/2326-6066.CIR-23-1094. https://pubmed.ncbi.nlm.nih.gov/39269445/

3. Bao, Zhaoshi, Li, Shouwei, Wang, Liang, Qiu, Xiaoguang, Jiang, Tao. 2023. PTPRZ1-METFUsion GENe (ZM-FUGEN) trial: study protocol for a multicentric, randomized, open-label phase II/III trial. In Chinese neurosurgical journal, 9, 21. doi:10.1186/s41016-023-00329-0. https://pubmed.ncbi.nlm.nih.gov/37443050/

4. Xia, Zhenkun, Ouyang, Dengjie, Li, Qianying, Yi, Wenjun, Zhou, Enxiang. 2019. The Expression, Functions, Interactions and Prognostic Values of PTPRZ1: A Review and Bioinformatic Analysis. In Journal of Cancer, 10, 1663-1674. doi:10.7150/jca.28231. https://pubmed.ncbi.nlm.nih.gov/31205522/