Age-dependent regulation of the tumorigenic potential of neoplastically transformed rat liver epithelial cells by the liver microenvironment.

Neoplastically transformed rat liver epithelial cell lines (GN6TF and GP7TB), which form tumors with short latency at s.c. or i.p. transplantation sites of syngeneic rats, did not form tumors or were weakly tumorigenic following transplantation into the livers of young adult rats and expressed increasing tumorigenicity in livers of increasingly aged rats. These results suggest that progressive alterations in the hepatic parenchyma with increasing age enabled tumor formation by providing a less suppressive microenvironment for expression of the tumorigenic phenotype. Age is widely recognized as a significant risk factor in the development of neoplasia; this study describes a model for investigation of the influence of age-dependent changes in the hepatic microenvironment on the development of hepatic cancer.