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 |
|---|---|
| Journal | Molecular Imaging |
| Volume | 18 |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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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
Cite this
The Development and Applications of a Dual Optical Imaging System for Studying Glioma Stem Cells. / Tai, Po An; Liu, Yen Lin; Wen, Ya Ting; Lin, Chien Min; Huynh, Thanh Tuan; Hsiao, Michael; Wu, Alexander T.H.; Wei, Li.
In: Molecular Imaging, Vol. 18, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Development and Applications of a Dual Optical Imaging System for Studying Glioma Stem Cells
AU - Tai, Po An
AU - Liu, Yen Lin
AU - Wen, Ya Ting
AU - Lin, Chien Min
AU - Huynh, Thanh Tuan
AU - Hsiao, Michael
AU - Wu, Alexander T.H.
AU - Wei, Li
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
KW - Btk inhibitor
KW - CD133
KW - dual optical imaging system
KW - glioma stem cells (GSCs)
KW - temozolomide resistance
UR - http://www.scopus.com/inward/record.url?scp=85071740726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071740726&partnerID=8YFLogxK
U2 - 10.1177/1536012119870899
DO - 10.1177/1536012119870899
M3 - Article
C2 - 31478435
AN - SCOPUS:85071740726
VL - 18
JO - Molecular Imaging
JF - Molecular Imaging
SN - 1535-3508
ER -