胶质瘤亚型中粘附性G蛋白偶联受体GPR133（ADGRD1）的表达谱分析
Expression profiling of the adhesion G protein-coupled receptor GPR133 (ADGRD1) in glioma subtypes.
作者信息
Frenster Joshua D, Kader Michael, Kamen Scott, Sun James, Chiriboga Luis, Serrano Jonathan, Bready Devin, Golub Danielle, Ravn-Boess Niklas, Stephan Gabriele, Chi Andrew S, Kurz Sylvia C, Jain Rajan, Park Christopher Y, Fenyo David, Liebscher Ines, Schöneberg Torsten, Wiggin Giselle, Newman Robert, Barnes Matt, Dickson John K, MacNeil Douglas J, Huang Xinyan, Shohdy Nadim, Snuderl Matija, Zagzag David, Placantonakis Dimitris G
机构信息
Departments of Neurosurgery, New York, New York, USA.
NYU Grossman School of Medicine, New York, New York, USA; Kimmel Center for Stem Cell Biology, NYU Grossman School of Medicine, New York, New York, USA.
出版信息
Neurooncol Adv. 2020 Apr 28;2(1):vdaa053. doi: 10.1093/noajnl/vdaa053. eCollection 2020 Jan-Dec.
BACKGROUND
Glioma is a family of primary brain malignancies with limited treatment options and in need of novel therapies. We previously demonstrated that the adhesion G protein-coupled receptor GPR133 (ADGRD1) is necessary for tumor growth in adult glioblastoma, the most advanced malignancy within the glioma family. However, the expression pattern of GPR133 in other types of adult glioma is unknown.
METHODS
We used immunohistochemistry in tumor specimens and non-neoplastic cadaveric brain tissue to profile GPR133 expression in adult gliomas.
RESULTS
We show that GPR133 expression increases as a function of WHO grade and peaks in glioblastoma, where all tumors ubiquitously express it. Importantly, GPR133 is expressed within the tumor bulk, as well as in the brain-infiltrating tumor margin. Furthermore, GPR133 is expressed in both isocitrate dehydrogenase (IDH) wild-type and mutant gliomas, albeit at higher levels in IDH wild-type tumors.
CONCLUSION
The fact that GPR133 is absent from non-neoplastic brain tissue but de novo expressed in glioma suggests that it may be exploited therapeutically.
背景
胶质瘤是一类原发性脑恶性肿瘤，治疗选择有限，需要新的治疗方法。我们之前证明，粘附性G蛋白偶联受体GPR133（ADGRD1）是成人胶质母细胞瘤肿瘤生长所必需的，胶质母细胞瘤是胶质瘤家族中最晚期的恶性肿瘤。然而，GPR133在其他类型成人胶质瘤中的表达模式尚不清楚。
方法
我们在肿瘤标本和非肿瘤尸体脑组织中使用免疫组织化学来分析成人胶质瘤中GPR133的表达情况。
结果
我们发现，GPR133的表达随世界卫生组织（WHO）分级增加而升高，并在胶质母细胞瘤中达到峰值，所有胶质母细胞瘤肿瘤均普遍表达该蛋白。重要的是，GPR133在肿瘤实体以及脑浸润性肿瘤边缘均有表达。此外，GPR133在异柠檬酸脱氢酶（IDH）野生型和突变型胶质瘤中均有表达，尽管在IDH野生型肿瘤中的表达水平更高。
结论
GPR133在非肿瘤脑组织中不存在，但在胶质瘤中从头表达，这一事实表明它可能具有治疗潜力。
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