Significance of perivascular tumour cells defined by CD109 expression in progression of glioma
Significance of perivascular tumour cells defined by CD109 expression in progression of glioma
复制标题
DOI：
10.1002/path.4981
复制
发表时间：
2017-12-01
影响因子：
7.3
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
--
作者：
Shiraki, Yukihiro;Mii, Shinji;Takahashi, Masahide
在神经胶质瘤的发展过程中，肿瘤细胞经常利用血管周围的微环境来促进它们的存活和对常规疗法的抵抗。其中一些细胞被认为是脑肿瘤干细胞（BTSC）;然而，由于神经胶质瘤的复杂性，血管周围肿瘤细胞的分子性质尚未明确。在这里，我们确定了CD 109，糖基磷脂酰肌醇锚定蛋白和多种信号传导途径的调节器，作为一个重要的调节器的进展较低级别的胶质瘤（世界卫生组织II/III级）的临床病理学和全基因组测序分析组织从人类胶质瘤。CD 109阳性血管周围肿瘤细胞的重要性不仅在人类低级别胶质瘤组织中得到证实，而且在重现人类胶质瘤的小鼠模型中也得到证实。有趣的是，从小鼠胶质瘤中分离的BTSC表达高水平的CD 109。CD 109阳性BTSC对用替莫唑胺处理的分化的胶质瘤细胞产生增殖作用。这些数据揭示了胶质瘤进展过程中肿瘤细胞在血管周围区域的重要性，并表明CD 109是该疾病的潜在治疗靶点。版权所有（C）2017大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
In the progression of glioma, tumour cells often exploit the perivascular microenvironment to promote their survival and resistance to conventional therapies. Some of these cells are considered to be brain tumour stem cells (BTSCs); however, the molecular nature of perivascular tumour cells has not been specifically clarified because of the complexity of glioma. Here, we identified CD109, a glycosylphosphatidylinositol-anchored protein and regulator of multiple signalling pathways, as a critical regulator of the progression of lower-grade glioma (World Health Organization grade II/III) by clinicopathological and whole-genome sequencing analysis of tissues from human glioma. The importance of CD109-positive perivascular tumour cells was confirmed not only in human lower-grade glioma tissues but also in a mouse model that recapitulated human glioma. Intriguingly, BTSCs isolated from mouse glioma expressed high levels of CD109. CD109-positive BTSCs exerted a proliferative effect on differentiated glioma cells treated with temozolomide. These data reveal the significance of tumour cells that populate perivascular regions during glioma progression, and indicate that CD109 is a potential therapeutic target for the disease. Copyright (C) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.