EFFECTS OF TGFB1 ON TUMOR MICROENVIRONMENT AND LIVER CANCER INITIATION

Abstract

Liver cancer is a global health problem. Over the last 20 years, despite the advancement in anti-cancer therapies, liver cancer-related death increased by as much as 50%. Liver cancer is a typical inflammation-associated cancer; with more than 90 % of cases arising in the context of hepatic inflammation. Interestingly, the pleiotropic molecule, TGFB1, lies in the center of this inflammatory cascade. Increased TGFB1 expression is observed in liver cancer patients, yet a conclusive role for the molecule in liver cancer is lacking. In this study, by using a combination of zebrafish cancer models and human liver disease samples, roles of TGFB1 were examined. TGFB1 was demonstrated to be responsible for polarizing neutrophils and macrophages to a pro-tumor profile in zebrafish. In addition, by generation of a tgfb1a transgenic zebrafish line, chronic and high level of tgfb1a induction in hepatocytes was shown to cause not only hepatocellular carcinoma but also cholangiocarcinoma.