Anti-tumor effects and Regulation of Wnt signaling pathway of adenovirus-mediated DKK3 in glioblastoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: The University of Tokushima
• Principal Investigator: MIZOBUCHI Yoshifumi 徳島大学, 大学病院, 講師 (80547993)
• Co-Investigator(Kenkyū-buntansha): MURE Hideo 徳島大学, 大学院医歯薬学研究部, 助教 (00624355) ; NAGAHIRO Shinji 徳島大学, 大学院医歯薬学研究部, 教授 (60145315) ; KAGEJI Teruyoshi 徳島大学, 病院, 特任教授 (70294684) ; KUWAYAMA Kazuyuki 四国こどもとおとなの医療センター, 臨床研究部, 脳神経外科医長 (50614236) ; NAKAJIMA Kohei 徳島大学, 病院, 助教 (40710554) ; HARA Keijirou 徳島大学, 病院, 助教 (60710340)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 脳腫瘍 / グリオブラストーマ / Wnt / DKK3 / 遺伝子治療

Outline of Final Research Achievements

The effect of the third member of the Dickkopf family (DKK3) in the Wnt pathway in glioblastoma remains unclear. We first demonstrated the non-specific interaction of Wnt3a and Wnt5a with the receptors LRP6 and ROR2 and the up-regulation of the Wnt pathway in glioblastoma cells. We used an adenovirus vector and found that an increase in DKK3 protein attenuated the expression of Wnt3a, Wnt5a and LRP6, but not of ROR2, and their interaction, thereby affecting both canonical- and non-canonical Wnt downstream cascades. This produced anti-tumor effects in GBM xenograft models. The suppression of Wnt pathways upstream by DKK3 may have promise for the treatment of glioblastoma.

Free Research Field

脳神経外科学