Division of Pulmonary Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Veterinary Physiology and Pharmacology, Texas A & M University, College Station, TX.
Hum Mol Genet. 2018 Dec 15;27(24):4169-4175. doi: 10.1093/hmg/ddy289.
Hemangiopericytoma (HPC) is a rare vascular tumor, which is thought to originate from pericytes. However, no direct evidence for the cell of origin has been found, and the mechanism of HPC tumorigenesis is poorly understood. Here we report that loss of the tumor suppressor gene Tsc2 in pericytes using a FoxD1 promoter driven cre allele (Foxd1tm1(GFP/cre) Amc, FoxD1GC) leads to the formation of HPC in multiple sites. Tsc2ffFoxD1GC mice had stunted growth with seizures and tail and hind limb tremor with a median survival of 110 days. They also showed recombination in brain, spinal cord, tongue, liver, intestine and skeletal muscle. Distinctive perivascular tumors consisting of cells with oval nuclei and scant cytoplasm were identified in multiple sites in all Tsc2ffFoxD1GC mice. Immunohistochemistry staining showed a high expression of phospho-S6-S240/244, a hallmark of activated mTORC1, as well as pericyte markers NG2 and vimentin in these tumors. In summary, we demonstrate that loss of Tsc2 in pericytes generates HPC, the first mouse model of HPC reported.
血管外皮细胞瘤（HPC）是一种罕见的血管肿瘤，被认为起源于周细胞。然而，尚未发现其起源细胞的确切证据，其肿瘤发生机制也知之甚少。在这里，我们报告使用 FoxD1 启动子驱动的 cre 等位基因（Foxd1tm1(GFP/cre) Amc，FoxD1GC）使周细胞中的肿瘤抑制基因 Tsc2 缺失，会导致多种部位的 HPC 形成。Tsc2ffFoxD1GC 小鼠生长迟缓，伴有癫痫发作和尾巴及后肢震颤，中位生存期为 110 天。它们还在脑、脊髓、舌、肝、肠和骨骼肌中表现出重组。在所有 Tsc2ffFoxD1GC 小鼠的多个部位均发现了由具有椭圆形核和稀少细胞质的细胞组成的独特血管周细胞瘤。免疫组织化学染色显示这些肿瘤中磷酸化 S6-S240/244 的高表达，这是激活的 mTORC1 的标志，以及周细胞标志物 NG2 和波形蛋白。总之，我们证明了周细胞中 Tsc2 的缺失会产生 HPC，这是首个报道的 HPC 小鼠模型。
