Proinflammatory Liver Cell Provides Mechanistic Insight into Liver Cancer
The ongoing story of how chronic inflammation drives cancer pathogenesis, tumor invasiveness, and metastasis is a long-established one. In the latest chapter, the role of chronic inflammation, with its main character in driving development of liver cancer – liver Kupffer cells – was examined.
“Liver Kupffer cells have crucial roles in mediating the inflammatory processes that promote liver cancer, but the mechanistic basis for their contributions is not fully understood,” the investigators wrote.
To meet their aim, the investigators first showed that when Kupffer cells express the protein TREM-1, they induce inflammation in the liver. Chronic inflammation was shown to be a crucial factor in the development and progression of liver cancer.When the researchers removed the Trem1 gene from mice, exposure to the known liver carcinogen ethylnitrosamine (DEN) did not induce tumor formation. Removal of TREM-1 also reduced activation of Kupffer cells by turning off the expression and activity of several proinflammatory mediators. Reducing TREM-1 activity altogether spared the liver from the excessive injury that is characteristic of DEN exposure.
“Together, our findings offer causal evidence that TREM-1 is a pivotal determinant of Kupffer cell activation in liver carcinogenesis, deepening mechanistic insights into how chronic inflammation underpins the development and progression of liver cancer,” the investigators concluded.