The Anti- and Pro- Tumor Activities of Hepatic Stellate Cells in Liver Disease

Dr. Rifaat Safadi

Hepatic stellate cells (HSC) are directly activated by CD8 and are susceptible for the NK-cell killing in a phagocytosis manner. Although cirrhosis state is a pre-cancer condition for hepatocellular carcinoma (HCC); the exact role of HSC in hemostasis of HCC tumorgenesis is not fully understood. Based on our preliminary data, anti-tumoral effect of HSC is suggested against HCC cells. In this study, we intend to evaluate the homeostatic balance of the interaction between HSC and HCC, in vitro and in vivo. For in vitro study we will use Lx2 cells as HSC line and Hep3B cells as hepatoma cell line expressing surface HBsAg and secreting alpha-feto-protein (αFP). HSC will be identified using the alpha-smooth-muscle-actin (αSMA) marker; Hep3B will be identified by staining the surface HBsAg. αSMA will be used as a marker of HSC activation. For in vivo study; Hepatic fibrosis will be induced in male Nude-nu mice. Six groups will include: (A) Fibrotic animals with intrahepatic Hep3B injection post-fibrosis (B) Naive animals with intrahepatic Hep3B injection, (C) Fibrotic animals with intrahepatic Hep3B injection prior to fibrosis (D) Fibrotic animals with abdominal Hep3B injection post-fibrosis and (E) Naive animals with abdominal Hep3B injection (F) Fibrotic animals with abdominal Hep3B injection prior to fibrosis. The findings of this study are expected to have broad implications for novel immunomodulatory strategies in patients with advanced liver disease.