Notch signaling contributes to the maintenance of both normal neural stem cells and patient-derived glioma stem cells
| Autor: | Hua Han, Gang Cheng, Ya-Ning Wei, Luo-An Fu, Fang Gao, Yi-Yang Hu, Liang Liang, Liang Li, Min-Hua Zheng |
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| Jazyk: | angličtina |
| Předmět: |
Adult
endocrine system Cancer Research Cellular differentiation Neurogenesis Notch signaling pathway Biology lcsh:RC254-282 Mice Neural Stem Cells Cancer stem cell Genetics Animals Humans Cells Cultured Cell Proliferation Receptors Notch Brain Neoplasms fungi Cell Differentiation Glioma lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Embryo Mammalian Neural stem cell Cell biology Mice Inbred C57BL Oncology Hes3 signaling axis Neoplastic Stem Cells Stem cell Adult stem cell Research Article Signal Transduction |
| Zdroj: | BMC Cancer BMC Cancer, Vol 11, Iss 1, p 82 (2011) |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-11-82 |
| Popis: | Background Cancer stem cells (CSCs) play an important role in the development and recurrence of malignant tumors including glioma. Notch signaling, an evolutionarily conserved pathway mediating direct cell-cell interaction, has been shown to regulate neural stem cells (NSCs) and glioma stem cells (GSCs) in normal neurogenesis and pathological carcinogenesis, respectively. However, how Notch signaling regulates the proliferation and differentiation of GSCs has not been well elucidated. Methods We isolated and cultivate human GSCs from glioma patient specimens. Then on parallel comparison with NSCs, we inhibited Notch signaling using γ-secretase inhibitors (GSI) and assessed the potential functions of Notch signaling in human GSCs. Results Similar to the GSI-treated NSCs, the number of the primary and secondary tumor spheres from GSI-treated GSCs decreased significantly, suggesting that the proliferation and self-renewal ability of GSI-treated GSCs were attenuated. GSI-treated GSCs showed increased differentiation into mature neural cell types in differentiation medium, similar to GSI-treated NSCs. Next, we found that GSI-treated tumor spheres were composed of more intermediate progenitors instead of CSCs, compared with the controls. Interestingly, although inhibition of Notch signaling decreased the ratio of proliferating NSCs in long term culture, we found that the ratio of G2+M phase-GSCs were almost undisturbed on GSI treatment within 72 h. Conclusions These data indicate that like NSCs, Notch signaling maintains the patient-derived GSCs by promoting their self-renewal and inhibiting their differentiation, and support that Notch signal inhibitor GSI might be a prosperous candidate of the treatment targeting CSCs for gliomas, however, with GSI-resistance at the early stage of GSCs cell cycle. |
| Databáze: | OpenAIRE |
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