Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

Guanqun Qiao; Qingquan Li; Gang Peng; Jun Ma; Hongwei Fan; Yingbin Li

doi:10.3969/j.issn.1673-5374.2013.25.007

Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

Neural Regen Res. 2013 Sep 5;8(25):2360-9. doi: 10.3969/j.issn.1673-5374.2013.25.007.

Authors

Guanqun Qiao¹, Qingquan Li¹, Gang Peng¹, Jun Ma¹, Hongwei Fan², Yingbin Li¹

Affiliations

¹ Department of Neurosurgery, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China.
² Department of Pharmacology, the Third Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu Province, China.

PMID: 25206546
PMCID: PMC4146040
DOI: 10.3969/j.issn.1673-5374.2013.25.007

Abstract

Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are still unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc(+)/SV40Tag(+)/Tet-on(+)) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cells and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cells were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibrillary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibrillary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibrillary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cells. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

Keywords: brain tumor; brain tumor stem cells; doxycycline; multidirectional differentiation; neural regeneration; neural stem cells; neuroregeneration; stem cells; subventricular zone; transgenic mouse model.