Brain Tumor Stem Cells Team
Principal Investigator: Dr Christopher Ang
Cancer Stem Cell Model of Glioma Tumorigenesis
Although malignant tumors are known to be composed of a variety of different cell types, this concept of cellular heterogeneity in the study and design of anti-cancer therapeutics has largely been ignored. Primary malignant brain tumors are devastating cancers with poor survival rates despite major advances in surgical technology and adjuvant therapies. Emerging evidence in recent years has established key culprit cells within the tumor mass - the "cancer stem cells", which are responsible for initiation and propagation of tumor growth. These cancer stem cells are notoriously resistant to radiation and chemotherapy. The latter adjuvant therapies, which preferentially target rapidly dividing cells thus end up eliminating the bulk of tumor cells but spare these stem cells which divide at a much slower rate.Our group has established a method of cryopreservation that facilitates the establishment of a brain tumor stem cell repository. We have isolated brain tumor stem cells from patient tumor samples, which are capable of re-creating tumor masses in mice. These implanted cells in the mouse brain eventually form tumors with morphology identical to that seen on pathological analysis of patient specimens. These tumor cells-of-origin display genetic profiles totally distinct from the tumor bulk. Importantly, different patients with similar tumor tissue pathology on microscopic examination display very different genetic profiles in their cells-of-origin, the cancer stem cells. This has major implications as current treatment strategies are largely decided based upon classification systems tailored according to morphological characteristics of the tumor. The different genetic profiles of such tumor stem cells might explain variability of treatment response and points to the existence of different genetic brain tumor subtypes which one is unable to discern based on current classification systems. As such, we now have a stable collection of such cells to enable investigative efforts in drug screening. Our lab is also engaged in deciphering chemoresistance mechanisms and in discovery of novel markers for identification of these cells.
Christopher trained in neurosurgery at the National Neuroscience Institute (NNI), Singapore and at the University of British Columbia in Vancouver, Canada. During his residency, he carried out bench research defining molecular mechanisms in oligodendrocyte development and myelination. He is currently a consultant neurosurgeon at the NNI with a sub-specialty practice in minimal access neurosurgery, neuro-oncology and neurotrauma / critical care. He also contributes to medical education as an Associate Professor at the Duke-National University of Singapore Graduate Medical School, where he co-directs the Brain and Behaviour programme.
1. Foong CS, Ng FS, Phong M, Toh TB, Chong YK, Tucker-Kellogg G, Campbell RM, Ang BT, Tang C. Cryopreservation of cancer-initiating cells derived from glioblastoma. Front Biosci (Schol Ed). 2011 Jan 1;3:698-708. PubMed PMID: 21196406.
2. Zhao H, Tang C, Cui K, Ang BT, Wong ST. A screening platform for glioma growth and invasion using bioluminescence imaging. Laboratory investigation. JNeurosurg. 2009 Aug;111(2):238-46. PubMed PMID: 19199503.
3. Wang C, Chang KC, Somers G, Virshup D, Ang BT, Tang C, Yu F, Wang H. Protein phosphatase 2A regulates self-renewal of Drosophila neural stem cells. Development. 2009 Jul;136(13):2287-96. Erratum in: Development.2009 Sep;136(17):3031. PubMed PMID: 19502489.
4. Chong YK, Toh TB, Zaiden N, Poonepalli A, Leong SH, Ong CE, Yu Y, Tan PB, See SJ, Ng WH, Ng I, Hande MP, Kon OL, Ang BT, Tang C. Cryopreservation of neurospheres derived from human glioblastoma multiforme. Stem Cells. 2009 Jan;27(1):29-39. PubMed PMID: 18845764; PubMed Central PMCID: PMC2729678.
5. Chua C, Zaiden N, Chong KH, See SJ, Wong MC, Ang BT, Tang C. Characterization of a side population of astrocytoma cells in response to temozolomide. JNeurosurg. 2008 Nov;109(5):856-66. PubMed PMID: 18976075.
6. Nie DY, Zhou ZH, Ang BT, Teng FY, Xu G, Xiang T, Wang CY, Zeng L, Takeda Y, Xu TL, Ng YK, Faivre-Sarrailh C, Popko B, Ling EA, Schachner M, Watanabe K, Pallen CJ, Tang BL, Xiao ZC. Nogo-A at CNS paranodes is a ligand of Caspr: possible regulation of K(+) channel localization. EMBO J. 2003 Nov 3;22(21):5666-78. PubMed PMID: 14592966; PubMed Central PMCID: PMC275427.7. Hu QD, Ang BT, Karsak M, Hu WP, Cui XY, Duka T, Takeda Y, Chia W, Sankar N, Ng YK, Ling EA, Maciag T, Small D, Trifonova R, Kopan R, Okano H, Nakafuku M, Chiba S, Hirai H, Aster JC, Schachner M, Pallen CJ, Watanabe K, Xiao ZC. F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell. 2003 Oct 17;115(2):163-75. PubMed PMID: 14567914.