Teicher Beverly A, Bagley Rebecca G, Rouleau Cecile, Kruger Ariel, Ren Yi, Kurtzberg Leslie
Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701, USA.
Ann Saudi Med. 2011 Mar-Apr;31(2):174-82. doi: 10.4103/0256-4947.78206.
Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone sarcomas occurring in young people. Rare-disease clinical trials can require global collaborations and many years. In vivo models that as accurately as possible reflect the clinical disease are helpful in selecting therapeutics with the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell lines developed over the past 45 years are described. Several of these have undergone genetic analysis and have been confirmed to be those of Ewing/PNET sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in understanding the biology of this disease in the mouse. The chromosomal translocation producing the EWS/FLI1 fusion transcript characterizes clinical Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a xenograft in immunodeficient mice. The A673 model has been used to study Ewing sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma clinical specimens express the cell surface protein endosialin. Several Ewing sarcoma cell lines, including the A673 line, also express cell surface endosialin when grown as subcutaneous tumor nodules and as disseminated disease; thus the A673 is a useful model for the study of endosialin biology and endosialin-directed therapies. With the advent of tools that allow characterization of clinical disease to facilitate optimal treatment, it becomes imperative, especially for rare tumors, to develop preclinical models reflecting disease subsets. Ewing PNET sarcomas are a rare disease where models are available.
尤因肉瘤/外周原始神经外胚层瘤（PNET）是一种发生于年轻人的罕见侵袭性骨肉瘤。罕见病临床试验需要全球合作且耗时多年。尽可能准确反映临床疾病的体内模型有助于筛选最有可能产生积极临床效果的治疗方法。本文描述了过去45年中开发的人尤因肉瘤/PNET细胞系。其中一些细胞系已经过基因分析，被证实为尤因肉瘤/PNET肉瘤细胞系。A673尤因肉瘤细胞系已被证明在理解小鼠体内这种疾病的生物学特性方面特别有用。产生EWS/FLI1融合转录本的染色体易位是临床尤因肉瘤的特征。表达这种基因特征的细胞系被证实为尤因肉瘤细胞系。A673尤因肉瘤细胞系在培养物中生长，并能在免疫缺陷小鼠体内形成异种移植瘤。A673模型已被用于研究尤因肉瘤的血管生成以及对抗血管生成药物的反应。许多尤因肉瘤临床标本表达细胞表面蛋白内唾液酸蛋白。包括A673细胞系在内的几种尤因肉瘤细胞系，在形成皮下肿瘤结节和发生播散性疾病时也表达细胞表面内唾液酸蛋白；因此，A673是研究内唾液酸蛋白生物学特性和内唾液酸蛋白导向疗法的有用模型。随着能够对临床疾病进行特征化描述以促进最佳治疗的工具的出现，开发反映疾病亚群的临床前模型变得势在必行，尤其是对于罕见肿瘤。尤因肉瘤/PNET肉瘤是一种有可用模型的罕见疾病。
