Ovine Pulmonary Adenocarcinoma: A Large Animal Model for Human Lung Cancer

Abstract

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.

Patología pulmonar en ovinos faenados del norte del departamento de Bolívar, Colombia

“…Con menor frecuencia se reporta el adenovirus bovino tipo 2, el adenovirus ovino tipo 1 y 5, el reovirus tipo 1 (lengua azul) (Linnerth-Petrik, Walsh, Bogner, Morrison, & Wootton, 2014; Youssef, Wallace, Dagleish, Cousens, & Griffiths, 2015) y los lentivirus de pequeños rumiantes -SRLV: el virus Maedi Visna (MVV) y el virus de la artritis y encefalitis caprina (AEC)- (Barquero et al, 2013;Belknap, 2002;López 2012). En patología comparada existe interés por el VSR para utilizar los corderos como modelo de estudio de la neumonía que afecta neonatos humanos (Ackermann, 2014) y por el virus del adenocarcinoma pulmonar (enfermedad de jaagsiekte), el cual se ha reportado por inmunohistoquímica en carcinomas pulmonares de humanos (Linnerth-Petrik et al, 2014;Youssef et al, 2015).…”

Phylogenetic analysis of Jaagsiekte sheep retrovirus (JSRV) in Iraqi Awassi sheep

“…When the head is lowered, a copious foamy exudate or discharge from both nares occurs, and a moist rale is heard. However, coughing is not typically noticeable during auscultation (7). The clinical symptoms progress gradually, culminating in severe dyspnea; frequently, pneumonia due to secondary bacterial infection can occur, followed by death in a few days (8,9).…”

<p>Possible Oncogenic Viruses Associated with Lung Cancer</p>

“…172 OPA is characterized by the multifocal mixed presentation of adenocarcinoma, with its early lesions having similarity to lepidic-predominant adenocarcinoma and its advanced lesions resembling adenocarcinoma with papillary or acinar characteristics. 173 JSRV infects and transforms bronchiolar and alveolar epithelial cells, namely type II pneumocytes and club cells. 174 The cellular receptor for JSRV is hyaluronidase-2 (Hyal2) and Hyal2 has been shown to mediate human cell entry of JSRV Env pseudotyped retroviral particles.…”