UT Southwestern researchers have found that a protein in the body’s innate immune system that responds to gut microbes can suppress the most common type of liver cancer. Therefore The study, published today in the journal eLife, determined that NLRP12, an innate immune sensor, has a protective effect against hepatocellular carcinoma (HCC), a deadly human cancer associated with chronic inflammation.
HCC is responsible for more than 80% of liver cancers in the U.S. It is the third-leading cause of cancer-related deaths worldwide and the ninth-leading cause in America; according to the National Cancer Institute. Because NLRP12 is a member of the NOD-like family of pattern recognition receptors that help the body sense microbes and other stimuli within the cell to regulate the innate immune response the body’s first line of defense against infection in multiple ways.
This latest work adds to a growing body of evidence connecting inflammation and the development of tumors in the liver. Because “In this study; we demonstrated that NLRP12 responds to gut microbes and plays a critical role in suppressing a common form of liver cancer;” said Dr. Hasan Zaki; Assistant Professor of Pathology at UT Southwestern and corresponding author of the study.
Major risk factors for HCC include hepatitis B or C viral infection; therefore chronic alcohol abuse, and nonalcoholic fatty liver disease, a condition increasing worldwide along with obesity. Although the precise mechanisms through which these conditions induce liver cancer are unknown; inflammation in the liver is consider a key player.
“Our study indicates that NLRP12 acts to suppress liver cancer by reducing inflammation and down regulating the signals involve in tumor progression;” said Dr. Zaki, whose laboratory conducted the experiments on mice and on human cells from liver cancer patients. Therefore After being expose to a chemical carcinogen; because mice that were missing the Nlrp12 (mouse version) gene showed higher levels of inflammation and increased tumor development compared with normal mice; the study showed.
To understand why this occurred; the researchers looked at the signals sent by tumor cells in mice with and without the Nlrp12 gene. Because They found that the JNK (c-Jun N-terminal kinase); pathway – previously shown to be associated with liver cancer – is highly active in liver tumors that lack Nlrp12, Dr. Zaki said.
The JNK pathway can be activate by a component of bacterial cell walls called lipopoly saccharide (LPS); he said. Both “good” bacteria which line the gut and aid in digestion and “bad” pathogenic bacteria such as the Salmonella or E. coli – can release LPS, Dr. Zaki explained.
The LPS can move from the gut to the liver via the bloodstream and contribute to inflammation by setting off the JNK and other signaling pathways. Such transport is much more common in chronically inflame livers such as those of people suffering from hepatitis or fatty liver disease; he said.