期刊
JOURNAL OF PATHOLOGY
卷 243, 期 4, 页码 468-480出版社
WILEY
DOI: 10.1002/path.4981
关键词
glioma; tumour microenvironment; brain tumour stem cells; CD109
资金
- Japan Society for the Promotion of Science (JSPS) [26221304, 26253073, 24590478, 16 K08731]
- Japan Agency for Medical Research and Development (AMED), Japan
- Nagoya University Hospital Funding for Clinical Development
- Grants-in-Aid for Scientific Research [24590478, 15H04719, 26253073, 17K16643, 16K19104, 15H05909, 16K08731] Funding Source: KAKEN
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.
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