Development of mouse models of angiosarcoma driven by p53 [RESEARCH ARTICLE]
ABSTRACT
Angiosarcomas are a rare group of tumours which have poor prognosis and limited treatment options. The development of new therapies has been hampered by a lack of good preclinical models. Here, we describe the development of an autochthonous mouse model of angiosarcoma driven by loss of p53 in VE-cadherin-expressing endothelial cells. Using Cdh5-Cre to drive recombination in adult endothelial cells, mice developed angiosarcomas with 100% penetrance upon homozygous deletion of Trp53 with a median lifespan of 325 days. In contrast, expression of the R172H mutant p53 resulted in formation of thymic lymphomas with a more rapid onset (median lifespan 151 days). We also used Pdgfrb-Cre-expressing mice, allowing us to target predominantly pericytes, as these have been reported as the cell of origin for a number of soft tissue sarcomas. Pdgfrb-Cre also results in low levels of recombination in venous blood endothelial cells in multiple tissues during development. Upon deletion of Trp53 in Pdgfrb-Cre-expressing mice (Pdgfrb-Cre, Trp53fl/fl mice), 65% developed lymphomas and 21% developed pleomorphic undifferentiated soft tissue sarcomas. None developed angiosarcomas. In contrast, 75% of Pdgfrb-Cre, Trp53R172H/R172H mice developed angiosarcomas, with 60% of these mice also developing lymphomas. The median lifespan of the Pdgfrb-Cre, Trp53R172H/R172H mice was 151 days. Re-implantation of angiosarcoma tumour fragments from Cdh5-Cre, Trp53fl/fl mice provided a more...
Source: DMM Disease Models and Mechanisms - Category: Biomedical Science Authors: Salter, D. M., Griffin, M., Muir, M., Teo, K., Culley, J., Smith, J. R., Gomez-Cuadrado, L., Matchett, K., Sims, A. H., Hayward, L., Henderson, N. C., Brunton, V. G. Tags: Cancer, Rare diseases RESEARCH ARTICLE Source Type: research
More News: Angiosarcoma | Biomedical Science | Cancer | Cancer & Oncology | Lymphoma | Rare Diseases | Sarcomas | Soft Tissue Sarcoma | Study | Undifferentiated Carcinoma