Development of combined cellular and molecular target-directed therapies for glioblastoma

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26893096
• Research Institution: Kanazawa University
• Principal Investigator: Pyko Ilya 金沢大学, がん進展制御研究所, 研究員 (00731853)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: glioblastoma / temozolomide / mesenchymal stem cells / GSK 3β

Outline of Annual Research Achievements

Studies in vitro and in animal model were carried out complementary to explore whether mesenchymal stem cells (MSCs) transplantation benefits to treatment of glioblastoma (GBM) by enhancing anti-tumor effect in combination with GSK3β inhibitors and temozolomide (TMZ). Our experiments showed that transplantation of MSCs and GSK3β inhibition synergizes for treatment of experimental GBM and that MSCs co-cultured with GBM cells participate in regulation of GBM stemness phenotype similar to that observed under GSK3β inhibition.
We examined the interaction between patient-derived GBM stem-like cells and adipose tissue-derived MSCs in the presence and absence of GSK3β inhibition and TMZ and its influence on GBM stemness phenotype. I found that the interaction of MSCs with GBM stem-like cells is enhanced by a combined treatment by GSK3β inhibitor. I have also observed by confocal time-lapse microscopy frequent phagocytosis-like cellular reactions enhanced by GSK3b inhibition of the patient-derived MSCs when they were interacting with primary GBM-SCs. These observations encouraged us to continue investigation of the biological mechanisms by which MSCs regulate GBM stemness phenotype under the control by GSK3βaddressing the role of cell-to-cell interactions including phagocytosis and local signals.

Research Progress Status

27年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

27年度が最終年度であるため、記入しない。

Research Products

• [Presentation] 大腸がん糖代謝特性におけるGSK3βの役割 (2015)
  • Author(s): 堂本 貴寛, 紙 健次郎, 廣瀬 まゆみ, Ilya V. Pyko, 土原 一哉, 曽我 朋義, 江角 浩安, 源 利成
  • Organizer: 第3回がんと代謝研究会
  • Place of Presentation: 金沢市・県立音楽堂
  • Year and Date: 2015-07-16 – 2015-07-17