Coleman W B, Wennerberg A E, Smith G J, Grisham J W
Department of Pathology, School of Medicine, University of North Carolina, Chapel Hill 27599.
Am J Pathol. 1993 May;142(5):1373-82.
Following intrahepatic transplantation in adult syngeneic Fischer 344 rats, diploid cultured rat liver epithelial cells (WB-F344), modified to carry the Escherichia coli beta-galactosidase reporter gene and/or the fluorescent membrane dye PKH26-GL, integrate into hepatic plates and acquire the size and nuclear structure of mature hepatocytes. Additionally, of two aneuploid, neoplastically transformed derivatives of WB-F344 cells, both of which produce aggressively growing tumors when transplanted subcutaneously, cells of one line (GN6TF) do not produce tumors in the liver but integrate into hepatic plates and morphologically differentiate. The other transformed line (GP7TB) retains tumorigenicity in the liver, but cells in the intrahepatic tumors are more differentiated morphologically than are tumors at subcutaneous sites. These results suggest that WB-F344 cells are stemlike cells for hepatocytes and that the hepatic microenvironment induces them to incorporate into hepatic plates and differentiate. Our results also suggest that the hepatic microenvironment regulates the differentiation of some neoplastically transformed hepatic stemlike cells, thereby eliminating or reducing their tumorigenic potential.
在成年同基因Fischer 344大鼠进行肝内移植后，经改造携带大肠杆菌β-半乳糖苷酶报告基因和/或荧光膜染料PKH26-GL的二倍体培养大鼠肝上皮细胞（WB-F344）整合到肝板中，并获得成熟肝细胞的大小和核结构。此外，WB-F344细胞的两种非整倍体、肿瘤性转化衍生物，皮下移植时均产生侵袭性生长的肿瘤，其中一个细胞系（GN6TF）的细胞在肝脏中不产生肿瘤，但整合到肝板中并发生形态分化。另一个转化细胞系（GP7TB）在肝脏中保留致瘤性，但肝内肿瘤中的细胞在形态上比皮下部位的肿瘤更分化。这些结果表明，WB-F344细胞是肝细胞的干细胞样细胞，并且肝脏微环境诱导它们整合到肝板中并分化。我们的结果还表明，肝脏微环境调节一些肿瘤性转化的肝干细胞样细胞的分化，从而消除或降低它们的致瘤潜力。
