Zajdela Ascitic Hepatoma As a Continuum for Tumor Cells in a Transitional State

Abstract

Previously, from the adhesive cell line of Zajdela rat ascitic hepatoma, we obtained daughter sublines of two types (holoclonal and meroclonal), the cells of which differed in morphology (fibroblast- and epithelium-like, respectively), clonogenicity in tests in vitro, and tumorigenicity in vivo. To identify the potential role of Zajdela hepatoma adherent cells in processes of epithelial–mesenchymal transition (EMT) and metastasis, we compared all its sublines with monolayer lines of other hepatocellular tumors by the parameters that determine invasive and migratory properties of the cells. We have established that the cells of the holoclonal sublines are characterized by an increased activity of matrix metalloproteinase (MMP) 1, individual type of migration, and high motility rate as compared with the cells of other lines. The cells of all monolayer lines of Zajdela hepatoma secreted active forms of MMP-9 and translocated the intracellular domain of epithelial cell adhesion molecule (EpCAM) to their nucleus, which indicates the acquisition of an invasive phenotype by the cells and activation of Wnt/β-catenin signaling pathway. Our results indicate that the clonal sublines that we obtained from Zajdela ascitic hepatoma are consisted of the cells in transitional states between the epithelial and mesenchymal phenotypes.