Jia Yinhang, Xu Shangchen, Han Guangxu, Wang Bao, Wang Zejun, Lan Chuanjin, Zhao Peng, Gao Meng, Zhang Yi, Jiang Wenhong, Qiu Biying, Liu Rui, Hsu Yi-Cheng, Sun Yi, Liu Chong, Liu Yingchao, Bai Ruiliang
Department of Physical Medicine and Rehabilitation of the Affiliated Sir Run Run Shaw Hospital AND Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.
Nat Biomed Eng. 2023 Mar;7(3):236-252. doi: 10.1038/s41551-022-00960-9. Epub 2022 Nov 14.
The water-selective channel protein aquaporin-4 (AQP4) contributes to the migration and proliferation of gliomas, and to their resistance to therapy. Here we show, in glioma cell cultures, in subcutaneous and orthotopic gliomas in rats, and in glioma tumours in patients, that transmembrane water-efflux rate is a sensitive biomarker of AQP4 expression and can be measured via conventional dynamic-contrast-enhanced magnetic resonance imaging. Water-efflux rates correlated with stages of glioma proliferation as well as with changes in the heterogeneity of intra-tumoural and inter-tumoural AQP4 in rodent and human gliomas following treatment with temozolomide and with the AQP4 inhibitor TGN020. Regions with low water-efflux rates contained higher fractions of stem-like slow-cycling cells and therapy-resistant cells, suggesting that maps of water-efflux rates could be used to identify gliomas that are resistant to therapies.
水选择性通道蛋白水通道蛋白4（AQP4）促进胶质瘤的迁移和增殖，并使其产生治疗抗性。在此，我们在胶质瘤细胞培养物、大鼠皮下和原位胶质瘤以及患者的胶质瘤肿瘤中发现，跨膜水流出率是AQP4表达的敏感生物标志物，可通过传统的动态对比增强磁共振成像进行测量。水流出率与胶质瘤增殖阶段相关，也与替莫唑胺和AQP4抑制剂TGN020治疗后啮齿动物和人类胶质瘤肿瘤内和肿瘤间AQP4异质性的变化相关。水流出率低的区域含有较高比例的干细胞样慢循环细胞和抗治疗细胞，这表明水流出率图谱可用于识别对治疗有抗性的胶质瘤。
