德国癌症研究中心刘海坤研究组的一项发现鉴定了休眠胶质瘤干细胞的标志物基因GPD1。该研究于2019年8月发表于国际学术期刊《细胞—干细胞》杂志上。

通过对小鼠神经干细胞(NSC)和BTSC的核糖体翻译谱分析，研究人员发现3-磷酸甘油脱氢酶1 (GPD1)特异性表达于BTSC而非NSC。GPD1在处于休眠中的BTSC群体中表达，这个群体在肿瘤边界处富集，导致化疗后的肿瘤复发。抑制GPD1延长了胶质母细胞瘤小鼠模型的存活时间，其在一定程度上通过改变细胞代谢和蛋白翻译来影响了BTSC的维持。代谢组学和脂质组学分析证实，GPD1 阳性的 BTSC与NSC的表达谱不同，这依赖于GPD1的表达。在人类胶质瘤中也观察到类似的GPD1表达模式和预后相关性。这项研究为治疗脑瘤提供了一个可能的治疗靶点，并对BTSC休眠的调控机制提供了新的见解。

据了解，脑瘤干细胞(BTSC)是一个耐化疗的群体，能够促进肿瘤生长和复发，但BTSC特异性标志物的缺乏阻碍了选择性靶向治疗，从而使驻留干细胞得以存活。

附：英文原文

Title: GPD1 Specifically Marks Dormant Glioma Stem Cells with a Distinct Metabolic Profile

Author: Patricia Rusu, Chunxuan Shao, Anna Neuerburg, Azer Aylin Acikgz, Yonghe Wu, Peng Zou, Prasad Phapale, Tchirupura S. Shankar, Kristina Dring, Steffen Dettling, Huiqin Krkel-Qu, Gzde Bekki, Barbara Costa, Te Guo, Olga Friesen, Magdalena Schlotter, Mathias Heikenwalder, Darjus F. Tschaharganeh, Bernd Bukau, Günter Kramer, Peter Angel, Christel Herold-Mende, Bernhard Radlwimmer, Hai-Kun Liu

Issue&Volume: Volume 25 Issue 2

Abstract: Brain tumor stem cells (BTSCs) are a chemoresistant population that can drive tumor growth and relapse, but the lack of BTSC-specific markers prevents selective targeting that spares resident stem cells. Through a ribosome-profiling analysis of mouse neural stem cells (NSCs) and BTSCs, we find glycerol-3-phosphate dehydrogenase 1 (GPD1) expression specifically in BTSCs and not in NSCs. GPD1 expression is present in the dormant BTSC population, which is enriched at tumor borders and drives tumor relapse after chemotherapy. GPD1 inhibition prolongs survival in mouse models of glioblastoma in part through altering cellular metabolism and protein translation, compromising BTSC maintenance. Metabolomic and lipidomic analyses confirm that GPD1 + BTSCs have a profile distinct from that of NSCs, which is dependent on GPD1 expression. Similar GPD1 expression patterns and prognostic associations are observed in human gliomas. This study provides an attractive therapeutic target for treating brain tumors and new insights into mechanisms regulating BTSC dormancy.

DOI: https://doi.org/10.1016/j.stem.2019.06.004

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30268-1