Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells
Glioblastoma cells with stem-like properties control brain tumour growth and recurrence. Here, we show that endogenous neural precursor cells perform an anti-tumour response by specifically targeting stem-like brain tumour cells. In vitro, neural precursor cells predominantly express bone morphogene...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 30, 2010
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| In: |
Brain
Year: 2010, Volume: 133, Issue: Pt 7, Pages: 1961-1972 |
| ISSN: | 1460-2156 |
| DOI: | 10.1093/brain/awq128 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/brain/awq128
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| Author Notes: | Sridhar Reddy Chirasani, Alexander Sternjak, Peter Wend, Stefan Momma, Benito Campos, Ilaria M. Herrmann, Daniel Graf, Thimios Mitsiadis, Christel Herold-Mende, Daniel Besser, Michael Synowitz, Helmut Kettenmann and Rainer Glass |
| Summary: | Glioblastoma cells with stem-like properties control brain tumour growth and recurrence. Here, we show that endogenous neural precursor cells perform an anti-tumour response by specifically targeting stem-like brain tumour cells. In vitro, neural precursor cells predominantly express bone morphogenetic protein-7; bone morphogenetic protein-7 is constitutively released from neurospheres and induces canonical bone morphogenetic protein signalling in stem-like glioblastoma cells. Exposure of human and murine stem-like brain tumour cells to neurosphere-derived bone morphogenetic protein-7 induces tumour stem cell differentiation, attenuates stem-like marker expression and reduces self-renewal and the ability for tumour initiation. Neurosphere-derived or recombinant bone morphogenetic protein-7 reduces glioblastoma expansion from stem-like cells by down-regulating the transcription factor Olig2. In vivo, large numbers of bone morphogenetic protein-7-expressing neural precursors encircle brain tumours in young mice, induce canonical bone morphogenetic protein signalling in stem-like glioblastoma cells and can thereby attenuate tumour formation. This anti-tumour response is strongly reduced in older mice. Our results indicate that endogenous neural precursor cells protect the young brain from glioblastoma by releasing bone morphogenetic protein-7, which acts as a paracrine tumour suppressor that represses proliferation, self-renewal and tumour-initiation of stem-like glioblastoma cells. |
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| Item Description: | Gesehen am 13.03.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1460-2156 |
| DOI: | 10.1093/brain/awq128 |