Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice
- Author
- Morvarid Farhang Ghahremani (UGent) , Enrico Radaelli, Katharina Haigh (UGent) , Sona Bartunkova (UGent) , Lieven Haenebalcke (UGent) , Jean-Christophe Marine (UGent) , Steven Goossens (UGent) and Jody Haigh (UGent)
- Organization
- 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.
- Keywords
- CELL-LINE, mouse model, GROWTH-FACTOR, ANGIOSARCOMA, TUMOR, P53, ANGIOGENESIS, ESTABLISHMENT, MODEL, TUMORIGENESIS, METASTASIS, autocrine, p53, VEGF, endothelial cell, hemangiosarcoma
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-5658593
- MLA
- Farhang Ghahremani, Morvarid, et al. “Loss of Autocrine Endothelial-Derived VEGF Significantly Reduces Hemangiosarcoma Development in Conditional P53-Deficient Mice.” CELL CYCLE, vol. 13, no. 9, 2014, pp. 1501–07, doi:10.4161/cc.28474.
- APA
- Farhang Ghahremani, M., Radaelli, E., Haigh, K., Bartunkova, S., Haenebalcke, L., Marine, J.-C., … Haigh, J. (2014). Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice. CELL CYCLE, 13(9), 1501–1507. https://doi.org/10.4161/cc.28474
- Chicago author-date
- Farhang Ghahremani, Morvarid, Enrico Radaelli, Katharina Haigh, Sona Bartunkova, Lieven Haenebalcke, Jean-Christophe Marine, Steven Goossens, and Jody Haigh. 2014. “Loss of Autocrine Endothelial-Derived VEGF Significantly Reduces Hemangiosarcoma Development in Conditional P53-Deficient Mice.” CELL CYCLE 13 (9): 1501–7. https://doi.org/10.4161/cc.28474.
- Chicago author-date (all authors)
- Farhang Ghahremani, Morvarid, Enrico Radaelli, Katharina Haigh, Sona Bartunkova, Lieven Haenebalcke, Jean-Christophe Marine, Steven Goossens, and Jody Haigh. 2014. “Loss of Autocrine Endothelial-Derived VEGF Significantly Reduces Hemangiosarcoma Development in Conditional P53-Deficient Mice.” CELL CYCLE 13 (9): 1501–1507. doi:10.4161/cc.28474.
- Vancouver
- 1.Farhang Ghahremani M, Radaelli E, Haigh K, Bartunkova S, Haenebalcke L, Marine J-C, et al. Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice. CELL CYCLE. 2014;13(9):1501–7.
- IEEE
- [1]M. Farhang Ghahremani et al., “Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice,” CELL CYCLE, vol. 13, no. 9, pp. 1501–1507, 2014.
@article{5658593,
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.}},
author = {{Farhang Ghahremani, Morvarid and Radaelli, Enrico and Haigh, Katharina and Bartunkova, Sona and Haenebalcke, Lieven and Marine, Jean-Christophe and Goossens, Steven and Haigh, Jody}},
issn = {{1538-4101}},
journal = {{CELL CYCLE}},
keywords = {{CELL-LINE,mouse model,GROWTH-FACTOR,ANGIOSARCOMA,TUMOR,P53,ANGIOGENESIS,ESTABLISHMENT,MODEL,TUMORIGENESIS,METASTASIS,autocrine,p53,VEGF,endothelial cell,hemangiosarcoma}},
language = {{eng}},
number = {{9}},
pages = {{1501--1507}},
title = {{Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice}},
url = {{http://doi.org/10.4161/cc.28474}},
volume = {{13}},
year = {{2014}},
}
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