International Journal of Cancer, 1 December 2018, DOI: https://doi.org/10.1002/ijc.31827

AIM2 deficiency reduces the development of hepatocellular carcinoma in mice

Claudia Martínez-Cardona, Beatriz Lozano-Ruiz, Victoria Bachiller, Gloria Peiró, Francisco Algaba-Chueca, Isabel Gómez-Hurtado, José Such, Pedro Zapater, Rubén Francés, and José Manuel González-Navajas

1 Alicante Institute for Health and Biomedical Research (ISABIAL-FISABIO), Hospital General Universitario de Alicante, Alicante, Spain

2 Biomedical Research Network for Hepatic and Digestive Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain

3 Department of Pharmacology, University Miguel Hernández, Elche, Spain

4 Pathology Department, Hospital General Universitario de Alicante, Alicante, Spain

5 Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

6 Department of Clinical Medicine, University Miguel Hernández, Elche, Spain

7 The Second Affiliated Hospital, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Sino-French Hoffman Institute, Guangzhou Medical University, Guangzhou, China

Abstract

Chronic liver inflammation is crucial in the pathogenesis of hepatocellular carcinoma (HCC). Activation of the inflammasome complex is a key inflammatory process that has been associated with different liver diseases, but its role in HCC development remains largely unexplored. Here we analyzed the impact of different inflammasome components, including absent in melanoma 2 (AIM2) and NOD‐like receptor family pyrin domain containing 3 (NLRP3), in the development of diethylnitrosamine (DEN)‐induced HCC in mice. Genetic inactivation of AIM2, but not NLRP3, reduces liver damage and HCC development in this model. AIM2 deficiency ameliorates inflammasome activation, liver inflammation and proliferative responses during HCC initiation. We also identified that AIM2 is highly expressed in Kupffer cells, and that AIM2‐mediated production of IL‐1β by these cells is enhanced after DEN‐induced liver damage. Our data indicate that AIM2 promotes inflammation during carcinogenic liver injury and that it contributes to genotoxic HCC development in mice, thereby recognizing AIM2 as a potential therapeutic target in this disease.

Link：https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.31827