Significance of perivascular tumour cells defined by CD109 expression in progression of glioma

• DOI: 10.1002/path.4981
• Publication Date: 2017-09-09T15:42:40Z
• Authors: Yukihiro Shiraki; Shinji Mii; Atsushi Enomoto; Hiroyuki Momota; Yi-Peng Han; Takuya Kato; Kaori Ushida; Akira Kato; Naoya Asai; Yoshiki Murakumo; Kosuke Aoki; Hiromichi Suzuki; Fumiharu Ohka; Toshihiko Wakabay...; Tomoki Todo; Seishi Ogawa; Atsushi Natsume; Masahide Takahashi
• Keywords: Mice, Knockout; 0301 basic medicine; Time Factors; Brain Neoplasms; Glioma; GPI-Linked Proteins; Neoplasm Proteins; 3. Good health; Dacarbazine; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; Antigens, CD; Disease Progression; Neoplastic Stem Cells; Temozolomide; Tumor Cells, Cultured; Tumor Microenvironment; Animals; Humans; Antineoplastic Agents, Alkylating; Cell Proliferation; Signal Transduction

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 © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.