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Exp Neurol. 2014 Oct;260:56-68. doi: 10.1016/j.expneurol.2013.01.027. Epub 2013 Jan 31.

Signals that regulate the oncogenic fate of neural stem cells and progenitors.

Author information

1
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
2
Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, USA; Department of Pathology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, USA.
3
Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, USA; Department of Neurology, Sandler Neurosciences Center, University of California, San Francisco, USA. Electronic address: Anders.Persson@ucsf.edu.

Abstract

Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors.

KEYWORDS:

Brain tumor; Glioma; Medulloblastoma; Neural stem cell; Progenitor; Reprogramming; miRNA

PMID:
23376224
PMCID:
PMC3758390
DOI:
10.1016/j.expneurol.2013.01.027
[Indexed for MEDLINE]
Free PMC Article

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