Abstract
Glioblastoma multiforme represents one of the deadliest brain tumor types, manifested by a high rate of recurrence and poor prognosis. The presence of glioma stem cells (GSCs) can repopulate the tumor posttreatment and resist therapeutics. A better understanding of GSC biology is essential for developing more effective interventions. We established a CD133 promoter-driven dual reporter, expressing green fluorescent protein (GFP) and firefly luciferase (CD133-LG), capable for in vitro and in vivo imaging of CD133+ GSCs. We first demonstrated the reporter enabled in vitro analyses of GSCs. DBTRG-05MG (Denver Brain Tumor Research Group 05) carrying CD133-LG (DBTRG-05MG-CD133-LG) system reported increased GFP/luciferase activities in neurospheres. Additionally, we identified and isolated CD133+/GFP+ cells with increased tumorigenic properties, stemness markers, Notch1, β-catenin, and Bruton’s tyrosine kinase (Btk). Furthermore, prolonged temozolomide (TMZ) treatment enriched GSCs (reflected by increased percentage of CD133+ cells). Subsequently, Btk inhibitor, ibrutinib, suppressed GSC generation and stemness markers. Finally, we demonstrated real-time evaluation of anti-GSC function of ibrutinib in vivo with TMZ-enriched GSCs. Tumorigenesis was noninvasively monitored by bioluminescence imaging and mice that received ibrutinib showed a significantly lower tumor burden, indicating ibrutinib as a potential GSC inhibitor. In conclusion, we established a dual optical imaging system which enables the identification of CD133+ GSCs and screening for anti-GSC drugs.
Original language | English |
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Journal | Molecular Imaging |
Volume | 18 |
DOIs | |
Publication status | Published - Jan 1 2019 |
Keywords
- Btk inhibitor
- CD133
- dual optical imaging system
- glioma stem cells (GSCs)
- temozolomide resistance
ASJC Scopus subject areas
- Biotechnology
- Molecular Medicine
- Biomedical Engineering
- Radiology Nuclear Medicine and imaging
- Condensed Matter Physics
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The Development and Applications of a Dual Optical Imaging System for Studying Glioma Stem Cells
Tai, P. (Contributor), Liu, Y. (Contributor), Wen, Y. (Creator), Lin, C. (Creator), Huynh, T. (Contributor), Hsiao, M. (Creator), Wu, A. T. (Creator) & Wei, L. (Creator), SAGE Journals, 2019
DOI: 10.25384/sage.c.4653470.v1, https://doi.org/10.25384%2Fsage.c.4653470.v1
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Supplementary_Figure_1_Characterization_of_U87MG - The Development and Applications of a Dual Optical Imaging System for Studying Glioma Stem Cells
Wen, Y. (Creator), Hsiao, M. (Creator), Huynh, T. (Contributor), Lin, C. (Creator), Tai, P. (Contributor), Wu, A. T. (Creator), Wei, L. (Creator) & Liu, Y. (Contributor), SAGE Journals, 2019
DOI: 10.25384/sage.9767339.v1, https://doi.org/10.25384%2Fsage.9767339.v1
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