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

摘要: Malignant transformation of the endothelium is rare, and hemangiosarcomas comprise only 1% all sarcomas. For this reason due to lack appropriate mouse models, genetic mechanisms malignant endothelial are poorly understood. Here, we describe a hemangiosarcoma model generated by deleting p53 specifically in hematopoietic lineages. This strategy led high incidence hemangiosarcoma, with an average latency 25 weeks. To study vivo roles autocrine or cell autonomous VEGF signaling initiation and/or progression hemangiosarcomas, genetically deleted sources model. We found that loss even single conditional allele results substantial rescue from transformation. These findings highlight important role threshold levels malignancies suggest new approach for treatment using targeted inhibition.