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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: Chirasani, Sridhar Reddy (Author) , Sternjak, Alexander (Author) , Wend, Peter (Author) , Momma, Stefan (Author) , Campos, Benito (Author) , Herrmann, Ilaria Marta (Author) , Graf, Daniel (Author) , Mitsiadis, Thimios (Author) , Herold-Mende, Christel (Author) , Besser, Daniel (Author) , Synowitz, Michael (Author) , Kettenmann, Helmut (Author) , Glass, Rainer (Author)
Format: Article (Journal)
Language:English
Published: May 30, 2010
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

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520 |a 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. 
650 4 |a Animals 
650 4 |a Bone Morphogenetic Protein 7 
650 4 |a Brain Neoplasms 
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650 4 |a Mice, SCID 
650 4 |a Neoplastic Stem Cells 
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650 4 |a Stem Cells 
650 4 |a Tumor Cells, Cultured 
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