Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts
Ferritin heavy chain as a molecular imaging reporter gene in glioma xenografts
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铁蛋白重链作为神经胶质瘤异种移植物中的分子成像报告基因
DOI：
10.1007/s00432-017-2356-z
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发表时间：
2017-06-01
影响因子：
3.6
通讯作者：
Liu, Fusheng
中科院分区：
文献类型：
--
作者：
Cheng, Sen;Mi, Ruifang;Liu, Fusheng
胶质瘤治疗在临床实践中的发展（如基因治疗）需要有效地在体内观察和跟踪胶质瘤细胞。人铁蛋白重链是磁共振成像中一个新的基因报告基因。本研究提出hFTH作为异种胶质瘤MR分子成像的报告基因。用携带hFTH和EGFP基因的包装慢病毒感染大鼠C6胶质瘤细胞，并通过荧光活化细胞分选获得细胞。用总铁试剂盒分析其载铁能力。分别在皮下和颅内建立胶质瘤裸鼠模型。然后，通过IVIS光谱成像系统进行体内肿瘤生物发光。在7T动物MRI扫描仪上进行MR成像分析。最后采用western blotting和组织学分析分析hFTH的表达。成功获得了携带hFTH和EGFP报告基因的稳定胶质瘤细胞。细胞内铁浓度升高，但不影响细胞增殖速率。过表达hFTH的胶质瘤细胞在体外和体内的t -2加权MRI上的信号强度均显著降低。EGFP荧光成像也可以检测到皮下和颅内胶质瘤异种移植物。此外，在携带hFTH报告基因的胶质瘤细胞中，转铁蛋白受体的表达显著增加。我们的研究表明，hFTH通过调节转铁蛋白受体的表达，在胶质瘤中有效地产生细胞MR成像造影剂。这可能是一个有用的报告基因，在细胞跟踪和磁共振分子成像的胶质瘤的诊断，基因治疗和肿瘤转移。
The development of glioma therapy in clinical practice (e.g., gene therapy) calls for efficiently visualizing and tracking glioma cells in vivo. Human ferritin heavy chain is a novel gene reporter in magnetic resonance imaging. This study proposes hFTH as a reporter gene for MR molecular imaging in glioma xenografts.Rat C6 glioma cells were infected by packaged lentivirus carrying hFTH and EGFP genes and obtained by fluorescence-activated cell sorting. The iron-loaded ability was analyzed by the total iron reagent kit. Glioma nude mouse models were established subcutaneously and intracranially. Then, in vivo tumor bioluminescence was performed via the IVIS spectrum imaging system. The MR imaging analysis was analyzed on a 7T animal MRI scanner. Finally, the expression of hFTH was analyzed by western blotting and histological analysis.Stable glioma cells carrying hFTH and EGFP reporter genes were successfully obtained. The intracellular iron concentration was increased without impairing the cell proliferation rate. Glioma cells overexpressing hFTH showed significantly decreased signal intensity on T-2-weighted MRI both in vitro and in vivo. EGFP fluorescent imaging could also be detected in the subcutaneous and intracranial glioma xenografts. Moreover, the expression of the transferritin receptor was significantly increased in glioma cells carrying the hFTH reporter gene.Our study illustrated that hFTH generated cellular MR imaging contrast efficiently in glioma via regulating the expression of transferritin receptor. This might be a useful reporter gene in cell tracking and MR molecular imaging for glioma diagnosis, gene therapy and tumor metastasis.