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Liver cancer linked to cellular repair pathway

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Liver cancer, or hepatocellular carcinoma, often develops in people with cirrhotic livers damaged by chronic infections, such as hepatitis, by alcohol abuse or other causes. It is rare in people with healthy livers. The cancer's incidence is rising in the United States, with an estimated 17,550 new cases diagnosed in 2005 and 15,420 deaths. One reason for the rising rates is the increasing prevalence of obesity, which raises the risk of liver cancer five- to six-fold, said Anna Mae Diehl, M.D., chief of Duke's gastroenterology division and senior author on the study.

The liver's attempts to repair itself and regenerate new tissue after injury can trigger the Hedgehog pathway. During embryonic development, Hedgehog tells cells where and when to grow. In adult tissue, it signals the body to grow new tissue. "If the liver is injured badly, it uses some of the same mechanisms to repair itself as a fetus uses in growing a liver," Diehl said.

The Hedgehog pathway is also linked to certain brain, skin and muscle cancers and has recently been implicated in cancers of the pancreas, esophagus, lungs and prostate. The work by the Duke and Johns Hopkins team now adds liver cancer to the growing body of evidence suggesting these cancerous tumors are generated by stem-like cells.

Stem-like cells in the liver require the Hedgehog pathway for survival, the researchers discovered. These primitive cells are similar to stem cells, but differ in basic ways involving cell reproduction. Hedgehog may lead to liver and other cancers because of over-activation of Hedgehog pathway's components or genetic mutations that accumulate in these components during tissue repair.

"Ordinarily, the process is very tightly regulated, but apparently something goes wrong in these cells and the pathway is not turned off. That's what conveys malignancy," Sicklick said.

Study co-authors include Yin-Xiong Li, Yi Qi, Kouros Owzar and Wei Chen of Duke University Me
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Source:Duke University Medical Center


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