Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice

Morvarid Farhang Ghahremani, Enrico Radaelli, Katharina Haigh, Sonia Bartunkova, Lieven Haenebalcke, Jean-Christophe Marine, Steven Goossens, Jody Jonathan Haigh

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1501-1507
Number of pages7
JournalCell Cycle
Volume13
Issue number9
DOIs
Publication statusPublished - 2014

Keywords

  • autocrine
  • endothelial cell
  • hemangiosarcoma
  • mouse model
  • p53
  • VEGF

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