New development of a functional analysis and the differentiation instruction therapy of the glioblastoma stem cells using in vivo light imaging

2015 Fiscal Year Final Research Report

• Project/Area Number: 25861280
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Ehime University
• Principal Investigator: Inoue Akihiro 愛媛大学, 医学(系)研究科(研究院), 助教 (20593403)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 脳腫瘍学

Outline of Final Research Achievements

In this study, we subcutaneously transplanted Oct-3/4-overexpressing human glioblastoma (U251/EGFP-Oct-3/4) cells into the right thighs of nude mice to evaluate the roles of Oct-3/4 in tumor angiogenesis. The conditioned media from U251/EGFP-Oct-3/4 cells significantly accelerated capillary-like tube formation compared with that of U251/EGFP cells. In comparison with U251/EGFP cells, U251/EGFP-Oct-3/4 cells had markedly elevated the expression of vascular endothelial growth factor mRNA under the control of hypoxia-inducible factor (HIF) 1α. In U251/EGFP-Oct-3/4 cells, enhanced protein expression and nuclear translocation of HIF1α were observed. Furthermore, we demonstrated that the involvement of AKT, an oncogenic signaling molecule, in the Oct-3/4 induced upregulation of HIF1α protein. Our findings suggest that Oct-3/4-expressing glioblastoma cells have the ability to adapt to low-oxygen environments within tumor masses by promoting tumor angiogenesis through AKT-HIF1 pathway.

Free Research Field

外科系臨床医学・脳神経外科学