Examining the gut-liver axis in liver cancer using organoid models. (10th July 2021)

• Record Type: Journal Article
• Authors: Shek, Dmitrii; Chen, Dishen; Read, Scott A.; Ahlenstiel, Golo
• Is Part Of: Cancer letters. Volume 510(2021)
• Page Start: 48
• Page End: 58
• Publication Date: 2021-07-10
• Subjects: Fibrosis -- Cirrhosis -- Alcoholic liver disease -- MAFLD -- NASH -- Intestinal permeability; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.04.008
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: The World Health Organization predicts that by 2030 liver cancer will cause 1 million deaths annually, thus becoming the third most lethal cancer worldwide. Hepatocellular carcinoma and cholangiocarcinoma are the two major primary cancer subtypes involving the liver. Both are often diagnosed late, and hence response to treatment and survival are poor. It is therefore of utmost importance to understand the mechanisms by which liver cancers initiate and progress. The causes of primary liver cancer are diverse, resulting primarily from obesity, chronic alcohol abuse or viral hepatitis. Importantly, both alcohol and high fat diet can promote intestinal permeability, enabling microbial translocation from the gut into the liver. As a result, these microbial antigens and metabolites exacerbate hepatic inflammation and fibrosis, increasing the risk of primary liver cancer. Organoids are primary, three-dimensional, stem cell derived liver models that can recapitulate many of the disease phenotypes observed in vivo . This review aims to summarize the advantages of organoid culture to examine the gut-liver axis with respect to cancer initiation and progression. In particular, the use of gut and liver organoid mono- and co-cultures together and with immune cell populations to best recapitulate disease mechanisms and develop therapeutic interventions. Highlights: Liver cancer is driven by chronic inflammation as a result of obesity, alcohol or chronic infection. Obesity, alcohol and portal hypertension due to cirrhosis cause intestinal permeability. Bacterial translocation exacerbates chronic liver disease via the gut-liver axis. Gut and liver organoids are stem cell derived models that recapitulate alcohol and fat-induced gut and liver disease. Co-culture studies can be used to study interactions between the gut, liver and immune system.