A Case of Cancer Identify Theft

Cholangiocarcinoma develops when hepatocytes morph

(RxWiki News) Scientists would have said it was impossible. But the human body does miraculous things - including cells switching identities, morphing into one another.

A rare and deadly form of liver cancer - cholangiocarcinoma - that was thought to form in the organ's bile ducts has been found to arise when liver cells morph into a completely different type of cell.

"Discuss your family cancer history with your doctor."

University of California, San Francisco scientists uncovered this transformation by turning on two genes that formed tumors in mice in a very unexpected way. This finding may open the door for the development of new drugs to target these genes.

Here's the biology of all this. The liver has two types of cells that live side-by-side. These are the hepatocytes, that makes up most of the liver tissue, and the biliary cells, which are found inside the bile ducts. They have different functions inside the liver.

It's long been thought that the most common form of liver cancer - hepatocellular carcinomas - start in the hepatocytes. The rare cholangiocarcinoma, they reasoned, started in the cells of the bile ducts, the biliary cells.

Senior study author, Holger Willenbring, PhD, an associate professor of surgery, a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, says that hepatocytes either make more of their own or something goes wrong and cancer forms.

This finding came about rather serendipitously when senior author, Xin Chen, PhD, an assistant professor of bioengineering and therapeutic sciences, was trying to make something go wrong by inducing liver cancer in mice.

She worked with two oncogenes, which are genes that trigger cancer. Instead of the hepatocytes producing liver cancer, the two genes induced cholangiocarcinoma. "We were very surprised," said Dr. Chen.

To try and understand what happened, her team surmised that some of the genes may have reprogrammed the liver cells.

They injected the suspected culprits into mice to boost the levels of the NOTCH gene, which is involved in forming bile ducts, and AKT which plays a role in many cancers.

Within 3 1/2 weeks, tumors had begun to develop in the mice, and scientists realized that indeed the cancer had formed in the biliary cells and not the hepatocytes.

“This highlights how readily one cell can be converted into another and how cancer can do it for you very efficiently,” Dr. Willenbring said.

“For us, it’s fairly shocking. It only took two oncogenes and it all happened in a few weeks.”

Dr. Chen and her team are now working with Genentech, Inc. to develop drugs that block the NOTCH and AKT genes.

This study was published July 16 in the Journal of Clinical Investigation.

The research was supported by the California Institute of Regenerative Medicine, National Institutes of Health, Deutsche Forschungsgemeinschaft and the China Scholarship Council.

No conflicts of interest were reported.

Review Date: 
July 17, 2012