Three-dimensional culture of an ovine pulmonary adenocarcinoma-derived cell line results in re-expression of surfactant proteins and Jaagsiekte sheep retrovirus

Johnson, Chassidy; Fan, Hung

doi:10.1016/j.virol.2011.03.018

Cited by 5 publications

(3 citation statements)

References 41 publications

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“…Some studies have therefore focused on the use of primary OPA tumor cells (62, 89, 90); however, extended in vitro culture of these cells typically leads to a cessation in virus production (89, 90). These alterations in JSRV expression can be either delayed or reversed when cells are cultured in a 3D environment (89, 91), indicating that 3D culture models may more accurately recreate the oncogenic events that occur in OPA. Lung tissue explants are another in vitro model that has been developed.…”

Section: Experimental Systems For Studying Opamentioning

confidence: 99%

Ovine Pulmonary Adenocarcinoma: A Unique Model to Improve Lung Cancer Research

et al. 2019

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Lung cancer represents a major worldwide health concern; although advances in patient management have improved outcomes for some patients, overall 5-year survival rates are only around 15%. In vitro studies and mouse models are commonly used to study lung cancer and their use has increased the molecular understanding of the disease. Unfortunately, mouse models are poor predictors of clinical outcome and seldom mimic advanced stages of the human disease. Animal models that more accurately reflect human disease are required for progress to be made in improving treatment outcomes and prognosis. Similarities in pulmonary anatomy and physiology potentially make sheep better models for studying human lung function and disease. Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer that is caused by the jaagsiekte sheep retrovirus. The disease is endemic in many countries throughout the world and has several features in common with human lung adenocarcinomas, including histological classification and activation of common cellular signaling pathways. Here we discuss the in vivo and in vitro OPA models that are currently available and describe the advantages of using pre-clinical naturally occurring OPA cases as a translational animal model for human lung adenocarcinoma. The challenges and options for obtaining these OPA cases for research purposes, along with their use in developing novel techniques for the evaluation of chemotherapeutic agents or for monitoring the tumor microenvironment in response to treatment, are also discussed.

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Section: Experimental Systems For Studying Opamentioning

confidence: 99%

Ovine Pulmonary Adenocarcinoma: A Unique Model to Improve Lung Cancer Research

et al. 2019

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“…The loss of virus expression over repeated passage in culture is accompanied by a gradual reduction in expression of markers of differentiated epithelial cells, including surfactant protein-C (a marker of type II pneumocytes) during extended culture (Archer et al 2007;Dobbs et al 1997;Jassim et al 1987;Suau et al 2006). Interestingly, the changes in cellular differentiation state, including JSRV expression, can be delayed or reversed using three-dimensional culture systems, suggesting that cell polarization may be important for maintaining the phenotype of these cells (Archer et al 2007;Johnson and Fan 2011;Johnson et al 2010). This suggests that JSRV expression may be dependent upon the differentiated state of the infected cell.…”

Section: In Vitro Cell Culture Modelsmentioning

confidence: 99%

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

et al. 2015

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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.

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“…This altered differentiation state in monolayer culture is mirrored by OPA tumor cells, which stop producing JSRV after a relatively low number of passages in vitro [ 41 ]. Interestingly, the expression of JSRV and of surfactant proteins can be reactivated by growing OPA tumor cells in a 3D culture system as spheres of polarized cells [ 42 ] and the differentiated phenotype of primary ovine lung cells can be prolonged for several passages in culture by growth on a 3D matrix [ 25 ]. These findings demonstrate that polarization of epithelial cells is important for maintaining their differentiated phenotype in vitro.…”

Section: Discussionmentioning

confidence: 99%

Jaagsiekte sheep retrovirus infection of lung slice cultures

et al. 2015

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BackgroundJaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA), a transmissible neoplastic disease of sheep. OPA is an economically important veterinary disease and is also a valuable naturally occurring animal model of human lung cancer, with which it shares a similar histological appearance and the activation of common cell signaling pathways. Interestingly, the JSRV Env protein is directly oncogenic and capable of driving cellular transformation in vivo and in vitro. Previous studies of JSRV infection in cell culture have been hindered by the lack of a permissive cell line for the virus. Here, we investigated the ability of JSRV to infect slices of ovine lung tissue cultured ex vivo.ResultsWe describe the use of precision cut lung slices from healthy sheep to study JSRV infection and transformation ex vivo. Following optimization of the culture system we characterized JSRV infection of lung slices and compared the phenotype of infected cells to natural field cases and to experimentally-induced OPA tumors from sheep. JSRV was able to infect cells within lung slices, to produce new infectious virions and induce cell proliferation. Immunohistochemical labeling revealed that infected lung slice cells express markers of type II pneumocytes and phosphorylated Akt and ERK1/2. These features closely resemble the phenotype of natural and experimentally-derived OPA in sheep, indicating that lung slice culture provides an authentic ex vivo model of OPA.ConclusionsWe conclude that we have established an ex vivo model of JSRV infection. This model will be valuable for future studies of JSRV replication and early events in oncogenesis and provides a novel platform for studies of JSRV-induced lung cancer.

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Three-dimensional culture of an ovine pulmonary adenocarcinoma-derived cell line results in re-expression of surfactant proteins and Jaagsiekte sheep retrovirus

Cited by 5 publications

References 41 publications

Ovine Pulmonary Adenocarcinoma: A Unique Model to Improve Lung Cancer Research

Ovine Pulmonary Adenocarcinoma: A Unique Model to Improve Lung Cancer Research

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

Jaagsiekte sheep retrovirus infection of lung slice cultures

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