INTERACTION OF HEPATOCYTES AND CHOLANGIOCYTES DURING LIVER TUMORINGENESIS IN ZEBRAFISH

Abstract

Hepatocellular carcinoma is a disease that not only depends on the genetic mutations but also on the cell interaction between tumor cells and other cells within the liver. Cholangiocytes as hepatic cells, play an important role during liver development, yet there is not much data on its role during liver tumorigenesis. In the current thesis, by using a kras transgenic zebrafish model of hepatocarcinogenesis, I characterized and deciphered the molecular mediators of cholangiocytes during hepatocarcinogenesis. I have identified Sphingosine 1 phosphate receptor 2 (S1pr2) and histamine receptors (H1hr and H2hr) respectively as a main receptors governing hepatocyte and cholangiocyte interaction during hepatocarcinogenesis and dissected the underlined molecular pathways. Finally, I studied the interaction between the two cells under chemical carcinogenic condition and observed a compensatory behavior between the two types of cells dependent on carcinogen dose. Targeting either S1pr2 or histamine receptors may be a promising strategy in cancer therapy.