Title: Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice
Authors: Ghahremani, Morvarid Farhang *
Radaelli, Enrico *
Haigh, Katharina
Bartunkova, Sonia
Haenebalcke, Lieven
Marine, Chris
Goossens, Steven #
Haigh, Jody J # ×
Issue Date: May-2014
Publisher: Landes Bioscience
Series Title: Cell Cycle vol:13 issue:9 pages:1501-1507
Abstract: Malignant transformation of the endothelium is rare, and hemangiosarcomas comprise only 1% of all sarcomas. For this reason and due to the lack of appropriate mouse models, the genetic mechanisms of malignant endothelial transformation are poorly understood. Here, we describe a hemangiosarcoma mouse model generated by deleting p53 specifically in the endothelial and hematopoietic lineages. This strategy led to a high incidence of hemangiosarcoma, with an average latency of 25 weeks. To study the in vivo roles of autocrine or endothelial cell autonomous VEGF signaling in the initiation and/or progression of hemangiosarcomas, we genetically deleted autocrine endothelial sources of VEGF in this mouse model. We found that loss of even a single conditional VEGF allele results in substantial rescue from endothelial cell transformation. These findings highlight the important role of threshold levels of autocrine VEGF signaling in endothelial malignancies and suggest a new approach for hemangiosarcoma treatment using targeted autocrine VEGF inhibition.
ISSN: 1538-4101
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
* (joint) first author
× corresponding author
# (joint) last author

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