Characterization of Lgr5+ cells using a transposon-induced glioblastoma mouse model and identification of novel therapeutic targets

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460488
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kyoto Pharmaceutical University (2014-2015); 愛知県がんセンター(研究所) (2013)
• Principal Investigator: Nakata Susumu 京都薬科大学, 薬学部, 准教授 (80590695)
• Co-Investigator(Kenkyū-buntansha): FUJITA Mitsugu 近畿大学医学部, 細菌学教室, 准教授 (40609997)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 癌幹細胞 / 脳腫瘍 / 膠芽腫 / Lgr5 / Wnt / Shh

Outline of Final Research Achievements

The Sleeping Beauty transposon-induced glioblastoma model was successfully introduced in the Lgr5-eGFP transgenic mouse. Precise collections of the mouse glioblastoma tissues were feasible. Several lines of neurosphere culture using a neural stem cell culture system derived from the mouse glioblastoma tissues were established. Higher Lgr5 expression levels in the GFP positive fraction were confirmed. The observations that the Lgr5 positive cells exerted higher tumorigenicity in vivo indicated that the cancer stem cell properties were enriched in the Lgr5 positive glioblastoma cells. Global gene expression analysis was performed, which identified the shh-pathway as a signal activated in the Lgr5 positive population and higher expression of CDKNs in Lgr5 negative population. Furthermore, Gli2 was identified as an indispensible factor for the glioblastoma stem cells.

Free Research Field

腫瘍学