Differentiation status of rat ductal cells and ethionine-induced hepatic carcinomas defined with surface-reactive monoclonal antibodies

To gain further insight into the differentiation of oval cells and their role in carcinogenesis, we have generated cell surface reactive monoclonal antibodies (MAbs) by a Balb/c nude mouse (nu/nu) immunization protocol. Three MAbs designated OC.4, OC.5, and OC.10 were generated from a mouse immunized with CDE6, an oval cell line established from oval cells induced by feeding a choline-deficient dirt containing 0.1% ethionine (CDE). These MAbs demonstrated stage specific expression in fetal liver and displayed strong reactivity with oval and bile duct epithelial cells. In general, oval cells displayed a more mature phenotype than fetal ductal cells, suggesting the existence in adult liver of more primitive ductal progenitors. A fourth MAb recognized a cytoplasmic antigen (OC.6) expressed by mucus-secreting hepatic ducts induced by CDE diet. Immunocytochemical analysis indicated that OC.4, OC.5, and OC.10 were also expressed on CDE-induced. OV6+ hepatocellular carcinomas (HCC) but not on OV6+ HCC induced by the Solt/Farber protocol. In most cases, CDE-induced, OV6+ I-ICC expressed early ductal developmental markers such as OC.10 but lacked those expressed at later stages (OC.5, OC.-l). These new MAb will be useful for characterizing HCC subpopulations with oval cell characteristics and For isolating biliary cells at antigenically defined stages during differentiation. ()C 2000 Academic Press.