A non-cell autonomous mouse model of CNS haemangioblastoma mediated by mutant KRAS

Haemangioblastoma is a rare malignancy of the CNS where vascular proliferation causes lesions due to endothelial propagation. We found that conditionally expressing mutant Kras , using Rag1-Cre, gave rise to CNS haemangioblastoma in the cortex and cerebellum in mice that present with highly vascular...

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Bibliographic Details
Published in:Scientific reports 2017-03, Vol.7 (1), p.44899-44899, Article 44899
Main Authors: Bao, Leyuan, Al-Assar, Osama, Drynan, Lesley F., Arends, Mark J., Tyers, Pam, Barker, Roger A., Rabbitts, Terence H.
Format: Article
Language:English
Subjects:
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Animals
Cell proliferation
Central nervous system
Cerebellar Neoplasms - genetics
Cerebellar Neoplasms - mortality
Cerebellar Neoplasms - pathology
Cerebellum
Disease Models, Animal
Endothelial cells
Gene Expression
Genes, ras
Genes, Reporter
Hemangioblastoma - genetics
Hemangioblastoma - mortality
Hemangioblastoma - pathology
Humanities and Social Sciences
Humans
Incidence
Interstitial cells
K-Ras protein
Malignancy
Mice
Mice, Transgenic
multidisciplinary
Mutants
Mutation
RAG1 protein
Rodents
Science
Stromal cells
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Description
Summary:Haemangioblastoma is a rare malignancy of the CNS where vascular proliferation causes lesions due to endothelial propagation. We found that conditionally expressing mutant Kras , using Rag1-Cre, gave rise to CNS haemangioblastoma in the cortex and cerebellum in mice that present with highly vascular tumours with stromal cells similar to human haemangioblastomas. The aberrant haemangioblastoma endothelial cells do not express mutant Kras but rather the mutant oncogene is expressed in CNS interstitial cells, including neuronal cells and progeny. This demonstrates a non-cell autonomous origin of this disease that is unexpectedly induced via Rag1-Cre expression in CNS interstitial cells. This is the first time that mutant RAS has been shown to stimulate non-cell autonomous proliferation in malignancy and suggests that mutant RAS can control endothelial cell proliferation in neo-vascularisation when expressed in certain cells.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep44899