AIM2 deficiency reduces the development of hepatocellular carcinoma in mice. Issue 11 (9th October 2018)

• Record Type: Journal Article
• Authors: Martínez‐Cardona, Claudia; Lozano‐Ruiz, Beatriz; Bachiller, Victoria; Peiró, Gloria; Algaba‐Chueca, Francisco; Gómez‐Hurtado, Isabel; Such, José; Zapater, Pedro; Francés, Rubén; González‐Navajas, José Manuel
• Is Part Of: International journal of cancer. Volume 143:Issue 11(2018)
• Page Start: 2997
• Page End: 3007
• Publication Date: 2018-10-09
• Subjects: AIM2 -- inflammasome -- HCC -- diethylnitrosamine -- inflammation; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31827
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Chronic liver inflammation is crucial in the pathogenesis of hepatocellular carcinoma (HCC), but the role of the inflammasome complex in HCC development remains largely unexplored. Here, the authors demonstrate that the inflammasome‐related receptor absent in melanoma 2 (AIM2), but not NLRP3, contributes to the development of chemically‐induced HCC in mice. The data show that AIM2 is highly expressed and functional in Kupffer cells, promotes inflammasome activation in the liver, and enhances inflammatory and proliferative responses during HCC‐associated liver damage. Thus, the study highlights a previously unrecognized role for AIM2 in promoting chemical hepatocarcinogenesis that could have important translational implications.