When cancer spreads to another organ, it most often moves to the liver.
When the cancer spreads to another organ, it most often moves to the liver, and now researchers at the University of Pennsylvania's Abramson Cancer Center say they know why. A new study published today in the journal Nature shows that liver cells — the liver's primary function cells — are at the center of the chain reaction, making them particularly sensitive to cancer cells. These liver cells respond to inflammation by activating a protein called STAT3, which in turn increases the production of other proteins, SAA, which then reshape the liver and produce the "soil" needed for cancer cells to "seed." The researchers showed that this process is stopped by using antibodies that block IL-6, an inflammatory signal that drives this chain reaction, which limits the likelihood that cancer will spread to the liver.
"The seed and soil hypothesis is widely accepted, but our research now shows that hepatocytes are the primary coordinators of this process," said senior author Gregory L. Beatty, Ph.D., an assistant professor of hematology, Ph.D., of oncology at the Perelman School of Medicine in Pennsylvania. Jae W. Lee, MD/Ph.D. The Beatty Labs candidate is the first author.
In this study, the team first used a mouse model (PDAC) of pancreatic ductal adenocarcinoma, the most common type of cancer of the pancreas, which is currently the third leading cause of cancer death in the United States. They found that almost all of the liver cells showed STAT3 activation in cancer mice, compared to less than 2 percent of the mouse liver cells without tumors. They then worked with investigators at the Mayo Clinic in Arizona and other colleagues in Pennsylvania to show that the same biology can be seen in pancreatic cancer as well as colon and lung cancer patients. The genetic deletion of STAT3 only in liver cells effectively prevents the liver's increased susceptibility to cancer inoculation in mice. The team worked further with researchers at the University of Kentucky to show that IL-6 controls STAT3 signaling in these cells and directs liver cells in the preparation of SAA,
"The liver is an important sensor in the body," Li said. "We found that liver cells sense inflammation and respond in a structured way that cancer uses to help it spread."
The study also found that IL-6 drives changes in the liver whether tumors are present or not, meaning that any disease associated with elevated IL-6 levels — such as obesity or cardiovascular disease — could affect how receptive the liver is to cancer. The researchers say this proves that treatments that target liver cells may be able to prevent cancer from spreading to the liver, which is the leading cause of cancer death. #Breeze Plan # #健康真探社 #
Further information: Hepatocytes guide the formation of pre-metastatic niches in the liver, Nature (2019). DOI：10.1038 / s41586-019-1004-y，https ：//www.nature.com/articles/s41586-019-1004-y
