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Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm

Rahman, Ruman; Heath, Rachel; Grundy, Richard

Authors

Rachel Heath

RICHARD GRUNDY richard.grundy@nottingham.ac.uk
Professor of Paediatric Neuro-Oncology



Abstract

Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering acceptance that brain tumour formation is a phenotypic outcome of dysregulated neurogenesis, with tumours viewed as abnormally differentiated neural tissue. In relation, there is accumulating evidence that brain tumours, similar to leukaemia and many solid tumours, are organized as a developmental hierarchy which is maintained by a small fraction of cells endowed with many shared properties of tissue stem cells. Proof that neurogenesis persists throughout adult life, compliments this concept. Although the cancer cell of origin is unclear, the proliferative zones that harbour stem cells in the embryonic, post-natal and adult brain are attractive candidates within which tumour-initiation may ensue. Dysregulated, unlimited proliferation and an ability to bypass senescence are acquired capabilities of cancerous cells. These abilities in part require the establishment of a telomere maintenance mechanism for counteracting the shortening of chromosomal termini. A strategy based upon the synthesis of telomeric repeat sequences by the ribonucleoprotein telomerase, is prevalent in ∼ 90% of human tumours studied, including the majority of brain tumours. This review will provide a developmental perspective with respect to normal (neurogenesis) and aberrant (tumourigenesis) cellular turnover, differentiation and function. Within this context our current knowledge of brain tumour telomere/telomerase biology will be discussed with respect to both its developmental and therapeutic relevance to the hierarchical model of brain tumourigenesis presented by the cancer stem cell paradigm.

Journal Article Type Article
Publication Date 2009-04
Journal Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Print ISSN 0925-4439
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 1792
Issue 4
Pages 280-288
APA6 Citation Rahman, R., Heath, R., & Grundy, R. (2009). Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm. BBA - Molecular Basis of Disease, 1792(4), 280-288. doi:10.1016/j.bbadis.2009.01.011
DOI https://doi.org/10.1016/j.bbadis.2009.01.011
Keywords Neurogenesis; Neural stem cell; Telomerase; Telomere; Brain tumour stem cell
Publisher URL https://www.sciencedirect.com/science/article/pii/S092544390900026X?via%3Dihub
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