Cerebral Palsy

Gliomas, the most frequent primitive CNS tumors, have been suggested to originate from astrocytes or from neural progenitor/stem cells. However, the precise identity of the cells at the origin of gliomas remains a matter of debate because no pre-neoplastic state has been yet identified. TGFalpha, an EGF family member, is frequently over-expressed in the early stages of glioma progression. We previously demonstrated that prolonged exposure of astrocytes to TGFalpha is sufficient to trigger their reversion to a neural progenitor-like state. To determine whether TGFalpha de-differentiating effects are associated with cancerous transforming effects, we grafted intra-cerebrally de-differentiated astrocytes. We show that these cells had the same cytogenomic profile as astrocytes, survived in vivo and did not give birth to tumors. When astrocytes de-differentiated with TGFalpha were submitted to oncogenic stress using gamma irradiation, they acquired cancerous properties: they were immortalized, showed cytogenomic abnormalities, and formed high-grade glioma-like tumors after brain grafting. In contrast, irradiation did not modify the lifespan of astrocytes cultivated in serum-free medium. Addition of TGFalpha after irradiation did not promote their transformation but decreased their lifespan. These results demonstrate that reversion of mature astrocytes to an embryonic state without genomic manipulation is sufficient to sensitize them to oncogenic stress.

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