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

Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA) in sheep. A major interest is elucidating the mechanism(s) of transformation by the viral envelope (Env) that functions as an oncogene. These studies would benefit from a cell line derived from type II pneumocytes that have maintained the differentiation state. In this study we used an OPA-derived cell line (JS7), which has lost structural and functional properties of type II pneumocytes, and no longer expresses JSRV when grown in 2-D monolayer culture. When JS7 cells were placed in 3-D culture using Matrigel, they grew as small spheres of polarized cells that re-expressed surfactant proteins characteristic of type II pneumocytes. Moreover, JS7 cells grown in 3-D re-expressed JSRV virus by several criteria. This study underscores the importance of the culture environment on maintaining the differentiation state of OPA tumor cells as well as expression of JSRV.