Youssef Gehad, Wallace William A H, Dagleish Mark P, Cousens Chris, Griffiths David J
Gehad Youssef, BSc, is a research scientist at the Moredun Research Institute, Edinburgh, UK. William A. H. Wallace, MBChB(Hons), PhD, FRCPE, FRCPath, is a consultant pathologist at the Royal Infirmary of Edinburgh and Honorary Reader in Pathology, Edinburgh University, UK; Mark P. Dagleish BVM&S, PhD, MRCVS, FRCPath, is Head of Pathology at the Moredun Research Institute, Edinburgh, UK. Chris Cousens, PhD, is a senior research scientist at the Moredun Research Institute, Edinburgh, UK, and David J. Griffiths, PhD, is a principal research scientist at the Moredun Research Institute, Edinburgh, UK.
ILAR J. 2015;56(1):99-115. doi: 10.1093/ilar/ilv014.
Lung cancer is the leading cause of cancer deaths worldwide. Recent progress in understanding the molecular pathogenesis of this disease has resulted in novel therapeutic strategies targeting specific groups of patients. Further studies are required to provide additional advances in diagnosis and treatment. Animal models are valuable tools for studying oncogenesis in lung cancer, particularly during the early stages of disease where tissues are rarely available from human cases. Mice have traditionally been used for studying lung cancer in vivo, and a variety of spontaneous and transgenic models are available. However, it is recognized that other species may also be informative for studies of cancer. Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by retrovirus infection and has several features in common with adenocarcinoma of humans, including a similar histological appearance and activation of common cell signaling pathways. Additionally, the size and organization of human lungs are much closer to those of sheep lungs than to those of mice, which facilitates experimental approaches in sheep that are not available in mice. Thus OPA presents opportunities for studying lung tumor development that can complement conventional murine models. Here we describe the potential applications of OPA as a model for human lung adenocarcinoma with an emphasis on the various in vivo and in vitro experimental systems available.
肺癌是全球癌症死亡的主要原因。近年来，在了解该疾病分子发病机制方面取得的进展带来了针对特定患者群体的新型治疗策略。还需要进一步研究以在诊断和治疗方面取得更多进展。动物模型是研究肺癌肿瘤发生的宝贵工具，尤其是在疾病早期，此时很难从人类病例中获取组织。传统上，小鼠被用于在体内研究肺癌，并且有多种自发和转基因模型可供使用。然而，人们认识到其他物种对于癌症研究也可能具有参考价值。绵羊肺腺瘤（OPA）是一种由逆转录病毒感染引起的绵羊自然发生的肺癌，它与人类腺癌有几个共同特征，包括相似的组织学外观和常见细胞信号通路的激活。此外，人类肺的大小和结构与绵羊肺的更接近，而与小鼠肺的差异较大，这有利于在绵羊身上开展一些小鼠无法进行的实验方法。因此，OPA为研究肺肿瘤发展提供了机会，可以补充传统的小鼠模型。在此，我们描述了OPA作为人类肺腺癌模型的潜在应用，重点介绍了现有的各种体内和体外实验系统。
