Microenvironment IL-1 Dictates the Fate of Hepatocellular Carcinogenesis in Mice

Hepatocellular Carcinoma (HCC) is the most common type of liver cancer in the world, which leads to more than 700,000 deaths a year, and is highly associated with chronic liver inflammation.

The IL-1 family of molecules consists of pro-inflammatory cytokines that mediates inflammation mainly through induction of local network of cytokines, chemokines and immune cell infiltration into affected sites.

In this project, we used a 2-steps chemical carcinogenesis model (using DEN and CCl₄­) for the development of murine HCC in mice with IL-1α or IL-1β deficiency, in comparison with control mice.

In all groups of mice, inflammatory foci were observed 90 days after the initial treatment with DEN, although in WT mice the number of foci was significantly higher than in IL-1 KO mice. We also noticed an increased proliferation rate of both hepatocytes and immune cells in liver tissues derived from WT mice compared to IL-1 KO mice, as well as high expression of glypican-3, a diagnostic marker of evolving HCCs, at this time interval. At a later stage of the experiments, we observed the formation of macroscopic tumors on the surface of livers, mostly in WT mice, with almost no tumor nodules development in the IL-1 KO mice. We found that in WT mice the number of glypican-3-expressing cells increased throughout the timeframe of the experiment, whereas in IL-1 KO mice only few glypican-3-expressing cells were observed only at later stages of the experiment. These findings indicate that the deficiency of either IL-1α or IL-1β leads to a protecting effect in inflammation-induced HCC liver cancer development.