Ductal adenocarcinoma of the pancreas (PDAC) is the most common form of pancreatic cancer and currently the third leading cause of cancer death in the world. When cancer spreads to another organ, it most often metastasizes to the liver.
    In a new study, researchers from Harvard University in the United States found that liver parenchymal cells, the major functional cells of the liver, are at the center of a continuous response that makes the liver especially sensitive to cancer cells. These cells respond to inflammation by activating STAT3, a protein that increases the production of SAA, which in turn reshapes the liver and creates the "soil" needed for cancer cells to grow.
    "The soil hypothesis is widely accepted, but our research now shows that liver cells are the primary coordinators of this process," said Dr. Gregory Beatty, professor of oncology at the university of Pennsylvania's perelman school of medicine.
    For the new study, Beatty and his team first used the PDAC rat model. They found that almost all liver cells in PDAC rats showed STAT3 activation, compared with less than 2 percent of liver cells in tumor-free rats. They then found that the same biological characteristics could be observed in patients with pancreatic cancer as well as those with caecum and lung cancer. The increased susceptibility of liver to cancer inoculation in rats was effectively prevented by removing only STAT3 from liver cells. They further found that il-6 controls STAT3 signaling in these cells and instructs liver cells to produce SAA, which ACTS as an alarm that attracts inflammatory cells and triggers a fibrotic response, building the "soil" needed for cancer vaccination.
    The study also found that il-6 promoted liver changes regardless of tumor presence, suggesting that any disease associated with elevated il-6 levels, such as obesity or cardiovascular disease may affect the liver's susceptibility to cancer. The researchers say this provides evidence that therapies that target liver cells may be able to stop the spread of cancer to the liver, which is the leading cause of cancer death.