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29 Acquisition of an invasive phenotype by bile ductule transitional cells in livers of rats treated with carcinogens and partial hepatectomy.

In studies on delineating orm bile canaliculi and desmosomes with hepatocytes and integrate into the hepatic cord where they either differentiate into nodular cells or into differentiated hepatocytes to repopulate the liver. To determine whether transitional cells utilize similar mechanisms to migrating and invading normal and malignant cells, we studied the relation of transitional cells to basal lamina and sinusoidal endothelium during their migration into the sinusoid and invasion into the liver parenchyma. Immunolocalization of cytokeratin 19 and dipeptidylpeptidase to identify transitional cells, of fibronectin for basal lamina and of von Willebrand factor for endothelium showed absence of basal lamina and discontinuity of endothelium at the site of contact between transitional cells and hepatocytes. Ultrastructural studies confirm these observations as well as the formation of bile canaliculi at the contact site. We also found that after the transitional cells completely integrated into the hepatic cord, endothelium neogenesis occurred as well as replication of transitional cells. We also infused the liver with a retroviral vector(E.coli beta-gal nls lacZ gene, G1nBgSvNa, from Gene Therapy Laboratory, USC) to label proliferating ductule cells. We found that transitional cells express beta-gal activity in the nucleus. These studies suggest that transitional cells translocate across extracellular matrix and endothelium presumably by mechanisms analogous to normal and malignant cellular invasion processes. Supported by NIH CA06576

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