Ptprz1-KO Mouse

Ptprz1, also known as protein tyrosine phosphatase receptor type Z, is involved in multiple cellular processes. It can interact with various molecules and is associated with pathways that influence cell proliferation, adhesion, migration, and epithelial-to-mesenchymal transition. It has been implicated in survival signaling and is of great importance in understanding tumor-related biological processes [6].

In glioblastoma, tumor-associated macrophages secrete pleiotrophin (PTN) which stimulates glioma stem cells through Ptprz1, promoting tumor growth. Disrupting Ptprz1 abrogates glioma stem cell maintenance and tumorigenic potential, and blocking the PTN-Ptprz1 signaling suppresses glioblastoma tumor growth and prolongs animal survival [1]. Anti-Ptprz1 RNA CAR T cells show antigen-specific and bystander antitumor activity in glioblastoma models, validating Ptprz1 as a target for glioblastoma treatment [2]. The PTPRZ1-MET fusion is associated with glioma progression, and drugs targeting this fusion may have therapeutic potential [3,4,7]. In clear cell renal cell carcinoma, Ptprz1 dephosphorylates and stabilizes RNF26, reducing the efficacy of tyrosine kinase inhibitors (TKIs) and PD-1 blockade, and inhibiting Ptprz1 enhances treatment sensitivity [5].

In conclusion, Ptprz1 plays a significant role in tumor-related biological processes, especially in glioblastoma and clear cell renal cell carcinoma. Studies on Ptprz1, including those using gene-knockout or conditional-knockout mouse models (implied by the in vivo functional studies), have provided insights into its role in disease progression and potential as a therapeutic target, which is crucial for developing new strategies to treat these diseases.

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. Wang, Yuxin, Suo, Jinghao, Wang, Zhixing, Liu, Yanwei, Peng, Xiaozhong. 2024. The PTPRZ1-MET/STAT3/ISG20 axis in glioma stem-like cells modulates tumor-associated macrophage polarization. In Cellular signalling, 120, 111191. doi:10.1016/j.cellsig.2024.111191. https://pubmed.ncbi.nlm.nih.gov/38685521/

5. Ma, Yongkang, Li, Wei, Liu, Xinlin, Liu, Wentao, Chen, Xiaobing. 2024. PTPRZ1 dephosphorylates and stabilizes RNF26 to reduce the efficacy of TKIs and PD-1 blockade in ccRCC. In Oncogene, 43, 3633-3644. doi:10.1038/s41388-024-03198-8. https://pubmed.ncbi.nlm.nih.gov/39443724/

6. 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/

7. Hu, Huimin, Mu, Quanhua, Bao, Zhaoshi, Wang, Jiguang, Jiang, Tao. 2018. Mutational Landscape of Secondary Glioblastoma Guides MET-Targeted Trial in Brain Tumor. In Cell, 175, 1665-1678.e18. doi:10.1016/j.cell.2018.09.038. https://pubmed.ncbi.nlm.nih.gov/30343896/