“Hedgehog” Find Could Lead to New Liver Cancer Tests and Treatments

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Source: University of Texas Medical Branch at Galveston Released: Mon

27-Feb-2006, 19:10 ET

“Hedgehog” Find Could Lead to New Liver Cancer Tests and Treatments

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LIVER CANCER HEPATITIS C HEDGEHOG HEPATOCELLULAR CARCINOMA

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A discovery by researchers at the University of Texas Medical Branch at

Galveston and their colleagues at China’s Sun Yat-Sen and Shandong

Universities could lead to new methods of diagnosing and treating the most

common form of liver cancer.

Newswise — A discovery by researchers at the University of Texas Medical

Branch at Galveston (UTMB) and their colleagues at China’s Sun Yat-Sen and

Shandong Universities could lead to new methods of diagnosing and treating

the most common form of liver cancer, hepatocellular carcinoma (HCC).

HCC, one of the hardest kinds of cancer to diagnose and treat, kills 14,000

people every year in the United States alone, primarily striking those

chronically infected by the hepatitis C virus. Its occurrence is increasing

faster than that of any other kind of cancer.

In an article published online in the journal Carcinogenesis, the scientists

report that HCC tissue samples taken from liver cancer patients and HCC

experimental cell lines both tested positive for a particular series of

biochemical reactions implicated in many other common cancers, including

those of the skin, prostate, brain, lung and breast.

Activation of this so-called “hedgehog pathway” helps spark the runaway cell

division that can lead to cancer, and substances that block it can cause

cancer cells to die and tumors to shrink. (The pathway takes its name from

one of its components, a signaling protein important to animal growth and

development that was discovered by fruit-fly geneticists; mutations in the

gene that produces this “hedgehog” protein cause the flies to develop a

spiky, hedgehog-like skin.)

“We think that hedgehog signaling activation is one of the major events

involved in the development of hepatocellular carcinomas, so identifying

hedgehog signaling would be an important way to diagnose HCC in its early

stages,” said the study’s lead author, Jingwu Xie, an associate professor of

pharmacology and toxicology at UTMB and member of the university’s Sealy

Center for Cancer Cell Biology. “Currently, since most HCCs are diagnosed

late, most patients are essentially not treatable. And if, as seems likely,

the hedgehog pathway is responsible for maintaining liver cells that serve

as the ‘seeds’ of hepatocellular carcinoma — what could be called cancer

stem cells — we should be able to target those with an optimum dose of

hedgehog inhibitors and, we hope, completely eliminate cancerous cells from

the liver.”

Xie’s UTMB group and the Sun Yat-Sen and Shandong University researchers

analyzed hepatocellular carcinoma tissue specimens taken from 115 Chinese

liver-cancer patients. They detected molecular markers for hedgehog pathway

activation in over half the specimens— a striking result, because the

hedgehog pathway is normally completely dormant in adult liver cells.

The scientists also found signs of hedgehog pathway activity in three of the

five lab-raised hepatocellular carcinoma cell lines they tested. When the

cell lines were treated with substances known to interfere with hedgehog

signaling — the plant-derived compound cyclopamine and antibodies to a

specific hedgehog protein known as “sonic hedgehog”— cancer cell

proliferation slowed, and in some cases cells actually underwent apoptosis,

a process of “programmed suicide.”

“Currently, there are no specific treatments for HCCs, and what treatments

are available cause liver damage,” Xie said. “The application of hedgehog

signaling inhibitors to HCC gives hope for effective HCC treatment. In

addition, now that we know hedgehog signaling activation is an early event

prompting HCC development, we should be able to create a transgenic mouse

with human genes, a model system that will help us identify other molecular

events leading to HCC tumors, which could help us develop other new drug and

diagnosis targets.”

http://www.newswise.com/articles/view/518355/

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