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Al B. Benson III, MD, FACP, FASCO

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Is Progression of Liver Cancer Aided by Kupffer Cell–Induced CXCL5 Expression?

By: Kayci Reyer
Posted: Tuesday, December 13, 2022

Research presented at the 2022 American Association for the Study of Liver Diseases (AASLD) Annual Meeting (Abstract 2216) suggests that CXCL5 expression triggered by lipopolysaccharide in liver carcinoma may be found in Kupffer cells alone. Kupffer cells are known to be associated with liver inflammation and disease progression.

“While the genetic and transcriptomic heterogeneity of liver cancer cells creates a major hurdle to liver cancer treatment, the difficulty is significantly elevated by the interaction between the malignant cells and liver inflammation,” noted Bangyan L. Stiles, PhD, of the University of Southern California, Los Angeles, and colleagues.

The study included data from patients with hepatocellular carcinoma whose information was available in the Gene Expression Omnibus database. Subtypes including hepatitis B–negative, hepatitis C–negative, and alcoholic and nonalcoholic steatohepatitis–related disease were represented. The upregulation of CXCL5 was observed in murine models as well as in Kupffer cells, and liver immune landscapes were evaluated using immunohistochemistry and flow cytometry. The only chemokine found to be upregulated in human hepatocellular carcinoma cells regardless of etiology was CXCL5. In disease tissues, immune cells—not tumor cells—were responsible for the creation of CXCL5.

Hepatic CXCL5 expression was found to be progressively upregulated in the PTEN-deleted mouse models, increasing up to almost 100-fold in mice with liver tumors. In the mice with liver tumors, Kupffer cells were found to be the catalyst for CXCL5 expression. Lipopolysaccharide induced Kupffer cells’ cytokine production. Kupffer cells targeted with lipopolysaccharide treatment experienced an almost 20-fold increase in CXCL5 production, although murine macrophage cell lines and primary peritoneal macrophages did not respond in kind to lipopolysaccharide treatment.

Disclosure: For full disclosures of the study authors, visit aasldpubs.onlinelibrary.wiley.com.


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