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

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 Wakabayashi, Tomoki Todo, Seishi Ogawa, Atsushi Natsume, Masahide Takahashi

研究成果: Article査読

23 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)468-480
ページ数13
ジャーナルJournal of Pathology
243
4
DOI
出版ステータスPublished - 12-2017
外部発表はい

All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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