Spontaneously transformed rat pancreatic epithelial oval cells give rise to ductal type adenocarcinomas

Oval epithelial cells that proliferate in the pancreas of the rats maintained on a copper-deficient diet are considered as stem cells with a potential to differentiate into hepatocytes. We isolated these oval cells from a copper-deficient rat and maintained these as a cell line in our laboratory. During 13th passage, oval cells showed increased growth and cellular pleomorphism and were analyzed for spontaneous transformation by anchorage-independent growth in soft agar and tumorigenicity in nude mice. Oval cells formed large colonies in soft agar and developed tumors in nude mice after subcutaneous transplantation. The tumors, by light and electron microscopy, showed features of well differentiated ductal-type adenocarcinomas. The phenotypic properties of these tumors included expression of neutral mucins, keratin filaments, carcinoembryonic antigen and glutathione S-transferase-π and absence of γ-glutamyltranspeptidase. The results of this study demonstrate that spontaneously transformed oval cells can form typical ductal-type adenocarcinomas. These observations are of particular interest, since bonafide ductal adenocarcinomas have not been described in the rat pancreas before.