Tumorigenicity in nude mice of dexamethasone-sensitive and -resistant, differentiated and dedifferentiated hepatoma cells.

The tumorigenicity of cell clones of the same histogenetic origin but with different dexamethasone sensitivities and states of differentiation was examined. Neither the degree of differentiation nor the glucocorticoid resistance influenced the tumor-forming capacity of Reuber rat hepatoma clones in nude mice. However, the tumorigenicity of independently isolated resistant clones maintained in vitro continuously for more than 1 year in the presence of a high concentration of dexamethasone decreased considerably. The fact that not only the differentiated but also the partially dedifferentiated and the dedifferentiated hepatoma cells grew in the form of tumors in nude mice made it possible to examine whether reexpression of the extinguished liver-specific functions occurs in the tumors. Reexpression of different liver-specific functions of the tumor cell lines derived from a partially dedifferentiated, dexamethasone-resistant clone was found, showing that in vivo tumor formation may induce differentiation.