在胶质瘤干细胞中表达的MET是多形性胶质母细胞瘤的有效治疗靶点。
MET Expressed in Glioma Stem Cells Is a Potent Therapeutic Target for Glioblastoma Multiforme.
作者信息
Tasaki Takayuki, Fujita Mitsugu, Okuda Takeshi, Yoneshige Azusa, Nakata Susumu, Yamashita Kimihiro, Yoshioka Hiromasa, Izumoto Shuichi, Kato Amami
机构信息
Department of Neurosurgery, Faculty of Medicine, Kindai University, Osaka, Japan.
Department of Microbiology, Faculty of Medicine, Kindai University, Osaka, Japan
出版信息
Anticancer Res. 2016 Jul;36(7):3571-7.
BACKGROUND
Glioblastoma multiforme (GBM) is the most frequent and the most malignant tumor among adult brain tumors. Previous reports led us to hypothesize that the proto-oncogene mesenchymal-epithelial transition (MET) expressed in glioma stem cell-like cells (GSCs) would be a potent therapeutic target for GBM.
PATIENTS AND METHODS
To address this question, we analyzed 113 original samples of tumors from patients based on immunohistochemistry. During this process, we were able to establish GSC lines from patients with GBM that were MET-positive and MET-negative. Using these cells, we tested the therapeutic impact of a MET inhibitor, crizotinib, both in vitro and in vivo.
RESULTS
Patients with MET-positive GBM exhibited poor survival. GSC-based experiments revealed that treatment with crizotinib, both in vitro and in vivo, exhibited therapeutic efficacy particularly against MET-positive GSCs.
CONCLUSION
Based on these findings, we conclude that MET expressed in GSCs might be a potent therapeutic target for GBM.
背景
多形性胶质母细胞瘤（GBM）是成人脑肿瘤中最常见且恶性程度最高的肿瘤。既往报道使我们推测，在胶质瘤干细胞样细胞（GSCs）中表达的原癌基因间充质-上皮转化（MET）可能是GBM的一个有效治疗靶点。
患者与方法
为解决这一问题，我们基于免疫组织化学分析了113例患者的肿瘤原始样本。在此过程中，我们成功从MET阳性和MET阴性的GBM患者中建立了GSC系。利用这些细胞，我们在体外和体内测试了MET抑制剂克唑替尼的治疗效果。
结果
MET阳性GBM患者的生存期较差。基于GSC的实验表明，克唑替尼在体外和体内治疗均显示出治疗效果，尤其是对MET阳性GSCs。
结论
基于这些发现，我们得出结论，GSCs中表达的MET可能是GBM的一个有效治疗靶点。
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