Faulty liver 'stem cells' might cause 40 per cent of liver cancers

In collaboration with the Press Association

US scientists have discovered stem cells in the liver, and found that they might be responsible for 40 per cent of liver cancers when they malfunction.

Scientists have spent a number of years looking for stem cells in the liver, but the latest study in the Proceedings of the National Academy of Sciences represents the first time that these have been found in the organ.

The breakthrough came when Lynt Johnson, a transplant surgeon at Georgetown University Medical Centre, suggested that Dr Lopa Mishra's research team look for stem cells in donor liver tissue that had recently been transplanted into patients with liver failure.

He argued that stem cells would be particularly active in this tissue as they would be rapidly generating new liver cells.

Acting on his suggestion, the researchers took liver biopsies from six surgery patients within four months of transplantation, and looked for cells producing certain proteins characteristic of stem cells.

For the first time, they were able to find normal stem cells in the tissue, at a rate of two to four stem cells per 30,000 to 50,000 cells.

Dr Mishra, lead author and director of cancer genetics at Georgetown's department of surgery, said: "These cells were working really hard, expressing all of these proteins in abundance. In our staining tests they looked like stars, surrounded by shells of cells that were also expressing TGF-beta (transforming growth factor beta) in order to make new liver cells."

The researchers then used the same technique to find cancer stem cells in tissue from ten liver cancer patients, and found that one of the apparently characteristic proteins, TGF-beta, was missing.

Dr Mishra revealed: "We found that all of these stem cells had lost TGF-beta. Without the brakes that TGF-beta puts on cancer, the stem cells had turned into bad guys."

The researchers also found evidence that a new experimental drug that shuts down stat3 - another protein associated with stem cells - may be effective against primary liver cancer, which accounts for around one per cent of newly-diagnosed cancers in the UK.

Preliminary results of the drug's effect on liver cancer cells from both mice and humans suggest that it dramatically inhibits cancer cells and the researchers are now trialling the drug on mice with liver cancer that are lacking TGF-beta.

Dr Mishra confirmed: "After locating the cancer stem cells that help control development of these tumours, we were able to find a potential vulnerability that might form the basis of a new treatment for this disease - which is greatly needed."

She concluded: "Now we have a way to think about treating liver cancer, and this is very exciting. Besides stat3, there are other proteins that are activated on cancer stem cells, so they might also offer us additional drug targets."