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


Type
Article
Change log
Authors
Bao, L 
Al-Assar, O 
Drynan, LF 
Arends, MJ 
Tyers, P 
Abstract

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.

Description
Keywords
CNS cancer, diseases of the nervous system
Journal Title
Scientific Reports
Conference Name
Journal ISSN
2045-2322
2045-2322
Volume Title
7
Publisher
Nature Publishing Group
Sponsorship
This work was supported by grants from the Medical Research Council (MR/J000612/1), the Wellcome Trust (099246/Z/12/Z) and Bloodwise (12051).