Epidemiological studies indicate that being overweight or obese is associated with increased cancer risk. The most dramatic effect of obesity on cancer risk has been noted for a common form of liver cancer called hepatocellular carcinoma or HCC. Modeling the effect of obesity in mice, researchers at the University of California, San Diego School of Medicine have conclusively demonstrated that obesity is tumor-promoting and have obtained evidence that this effect depends on induction of low-grade, chronic inflammation.
Their results, published January 22 by the journal Cell, may suggest novel therapy to prevent HCC development in obese men who suffer from chronic liver disease.
Michael Karin, PhD, Distinguished Professor of Pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, who led the study, found that obesity enhanced the development of HCC by stimulating the production of tumor-promoting cytokines interleukin-6 (Il-6) and tumor necrosis factor (TNF) that also cause chronic inflammation. Production of these signaling molecules, which are elevated in obese mice and in humans, causes inflammation of the liver and activation of a tumor-promoting transcription factor, a protein called STAT3. This protein in turn activates the formation and growth of liver cancer.
The primary role of TNF is in the regulation of immune cells, but its deregulated production can cause diseases such as rheumatoid arthritis or Crohn's disease. Ironically, while TNF was also tested for its ability to kill cancer, its chronic production was found to actually enhance tumor development.
IL-6 is known to be involved in the pathogenesis of rheumatoid arthritis, but previous work in the Karin lab has shown that IL-6 also contributes to the chronic inflammation that leads to liver cancer. HCC a devastating complication of chronic liver disease and inflammation caused by risk factors such as hepatitis B and C viruses, o
|Contact: Debra Kain|
University of California - San Diego