Aim: Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in a background of chronic liver disease and prolonged inflammation. A major contributor in the complex molecular pathogenesis of HCC is the highly intertwined cross-talk between the tumor and the surrounding stromal cells, such as hepatic stellate cells, endothelial cells, macrophages and other immune cells. These tumor-stroma interactions actively fuel tumor growth and modulate the hepatic microenvironment to benefit tumor invasion and disease progression. Platelets have been reported to interact with different cell types in the tumor microenvironment, including tumor cells, stellate cells and macrophages.
Materials and methods: Mice were treated with hepatocarcinogenic compound diethylnitrosamine for 25 weeks to induce HCC in the background of fibrosis and inflammation. From week 10, anti-platelet drug Clopidogrel was added to the drinking water and mice were given ad libitum access.
Key findings: In this study, we show that activated platelets promote tumor cell proliferation and contribute to the adverse tumor-stroma cross-talk that fuels tumor progression. We also show that inhibiting platelet activation with the P2Y12-inhibitor Clopidogrel decreases the number of tumors in a chemically induced mouse model for HCC.
Significance: These results suggest an important role for platelets in the pathogenesis of HCC and that the use of anti-platelet drugs may be therapeutically relevant for patients with liver cancer.
Keywords: Fibrosis; Hepatocellular carcinoma; P2Y12; Platelets.
Copyright © 2021. Published by Elsevier Inc.