PUBLICATION
A screening platform for glioma growth and invasion using bioluminescence imaging
- Authors
- Zhao, H., Tang, C., Cui, K., Ang, B.T., and Wong, S.T.
- ID
- ZDB-PUB-090217-14
- Date
- 2009
- Source
- Journal of neurosurgery 111(2): 238-246 (Journal)
- Registered Authors
- Wong, Stephen T.C.
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Movement
- Disease Progression
- Glioblastoma/pathology*
- Humans
- Luminescent Measurements/methods*
- Neoplasm Invasiveness/genetics
- Neoplasm Invasiveness/pathology*
- Oligonucleotide Array Sequence Analysis
- Purines/pharmacology
- Transplantation, Heterologous
- Tumor Cells, Cultured
- Zebrafish
- PubMed
- 19199503 Full text @ J. Neurosurg.
Citation
Zhao, H., Tang, C., Cui, K., Ang, B.T., and Wong, S.T. (2009) A screening platform for glioma growth and invasion using bioluminescence imaging. Journal of neurosurgery. 111(2):238-246.
Abstract
Object The study of tumor cell growth and invasion in cancer biology is often limited by the inability to visualize tumor cell behavior in real time in animal models. The authors provide evidence that glioma cells are heterogeneous, with a subset responsible for increased invasiveness. The use of bioluminescence (BL) imaging to investigate dynamic aspects of glioma progression are discussed. Methods Glioblastoma multiforme-initiating cells were generated under conditions typically used to sustain neural stem cells. The invasiveness potential was determined using a Matrigel chamber. The presence of an "invasiveness gene signature" that correlated with patient survival outcome was ascertained through microarray gene expression analysis. To measure invasiveness, the authors devised a method focussed on BL imaging and tested it in vitro and in vivo using a zebrafish xenograft model. Bioluminescence imaging signals were verified using known inhibitors of glioma growth: AEE788, N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester, and compound E. Results The authors' data support the idea that glioblastoma multiforme-initiating cells are heterogeneous and possess an invasive subset; BL imaging was used as a readout method to assess this invasive subset. The in vitro data obtained using a known glioma growth inhibitor, AEE788, showed that BL imaging could detect cellular movement and invasion even before overall cell death was detectable on conventional viability assays. Further work using a zebrafish tumor xenograft model supported the efficacy of BL imaging in monitoring changes in tumor load. Conclusions The authors used optically transparent zebrafish and high-resolution confocal imaging to track tumor growth in vivo and demonstrate the efficacy of this model for screening antitumor and antiangiogenic compounds. The integration of zebrafish transgenic technology into human cancer biological studies may aid in the development of cancer models targeting specific organs, tissues, or cell types within tumors. Zebrafish could also provide a cost-effective means for the rapid development of therapeutic agents directed at blocking tumor growth and invasion.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping