Brandt Laura P, Albers Joachim, Hejhal Tomas, Pfundstein Svende, Gonçalves Ana Filipa, Catalano Antonella, Wild Peter J, Frew Ian J
Institute of Physiology, University of Zurich, Zurich, Switzerland.
Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Oncotarget. 2018 Apr 13;9(28):19753-19766. doi: 10.18632/oncotarget.24831.
Soft tissue sarcomas are rare mesenchymal tumours accounting for 1% of adult malignancies and are fatal in approximately one third of patients. Two of the most aggressive and lethal forms of soft tissue sarcomas are angiosarcomas and undifferentiated pleomorphic sarcomas (UPS). To examine sarcoma-relevant molecular pathways, we employed a lentiviral gene regulatory system to attempt to generate models that reflect common molecular alterations of human angiosarcoma and UPS. Mice were intraveneously injected with MuLE lentiviruses expressing combinations of shRNA against , , and with or without expression of , or . The systemic injection of an ecotropic lentivirus expressing oncogenic together with the knockdown of or was sufficient to initiate angiosarcoma and/or UPS development, providing a flexible system to generate autochthonous mouse models of these diseases. Unexpectedly, different mouse strains developed different types of sarcoma in response to identical genetic drivers, implicating genetic background as a contributor to the genesis and spectrum of sarcomas.
软组织肉瘤是罕见的间充质肿瘤，占成人恶性肿瘤的1%，约三分之一的患者会因此死亡。两种最具侵袭性和致命性的软组织肉瘤是血管肉瘤和未分化多形性肉瘤（UPS）。为了研究与肉瘤相关的分子途径，我们采用了慢病毒基因调控系统，试图建立反映人类血管肉瘤和UPS常见分子改变的模型。给小鼠静脉注射表达针对、、和的shRNA组合的MuLE慢病毒，同时有或没有、或的表达。全身注射表达致癌的嗜亲性慢病毒并敲低或，足以引发血管肉瘤和/或UPS的发展，为生成这些疾病的原位小鼠模型提供了一个灵活的系统。出乎意料的是，不同的小鼠品系对相同的基因驱动因素产生了不同类型的肉瘤，这表明遗传背景是肉瘤发生和谱系的一个促成因素。
