Pancreatic cancer is one of the deadliest forms of cancer in the world. One reason it is so dangerous is that it often grows silently for a long time before symptoms appear.
By the time many patients receive a diagnosis, the cancer has already spread beyond the pancreas to other organs. Once this happens, treatment becomes much more difficult, and survival rates drop sharply.
Now, scientists at the University of California, San Francisco (UCSF) have made an important discovery that could help explain how pancreatic cancer spreads throughout the body. Their findings, published on May 21 in the journal Nature, reveal that a protein called PCSK9 plays a key role in helping cancer cells survive and grow in different organs.
The discovery provides new insight into one of the biggest challenges in cancer treatment: metastasis.
Metastasis occurs when cancer cells break away from the original tumor and travel through the bloodstream or lymphatic system to establish new tumors in distant organs. Most cancer-related deaths occur because of metastasis rather than the original tumor itself.
Scientists have long known that pancreatic cancer commonly spreads to the liver and lungs. However, they did not fully understand why certain cancer cells seem to prefer one organ over another. The UCSF research team wanted to uncover the biological mechanisms behind this process.
To investigate, the researchers used information from MetMap, a large research project developed by the Broad Institute. MetMap tracks how different cancer cell lines spread throughout the body and which organs they are most likely to colonize.
By studying pancreatic cancer cells that preferred either the liver or the lungs, researchers hoped to identify the factors responsible for these differences.
Their analysis led them to PCSK9, a protein already known for its role in cholesterol regulation. PCSK9 has attracted significant medical attention in recent years because drugs that block the protein are used to lower cholesterol levels and reduce the risk of heart disease.
The researchers discovered that PCSK9 also influences how pancreatic cancer cells obtain and use cholesterol. Cholesterol is often associated with heart disease, but it is also an essential substance that cells need to survive. Cells use cholesterol to build membranes, produce hormones, and support many important biological functions.
The study found that pancreatic cancer cells adapt differently depending on the environment they enter. The liver naturally contains abundant cholesterol. When cancer cells have low levels of PCSK9, they can easily absorb cholesterol from their surroundings in the liver, helping them survive and grow.
The situation is different in the lungs. The lung environment contains less readily available cholesterol and higher oxygen levels. The researchers found that cancer cells with high levels of PCSK9 respond by producing their own cholesterol. These cells also create protective molecules that help them cope with the oxygen-rich conditions found in lung tissue.
Perhaps the most surprising finding came when researchers genetically altered pancreatic cancer cells that normally spread to the liver. By increasing PCSK9 levels, they were able to change the behavior of the cells. Instead of moving toward the liver, the modified cancer cells began spreading to the lungs.
This result suggests that PCSK9 is far more than a simple marker associated with cancer spread. It appears to actively control how cancer cells adapt to different organs and determine where they can successfully establish new tumors.
Dr. Rushika Perera, the senior author of the study and a leading cancer biologist at UCSF, explained that cancer cells survive by adapting to unfamiliar environments throughout the body. The team’s findings show that pancreatic cancer uses PCSK9 as a tool to help make these adaptations possible.
The discovery could have important implications for future cancer treatments. If researchers can find ways to block or alter PCSK9 activity in cancer cells, they may be able to interfere with the metastatic process. In theory, this could make it more difficult for cancer cells to survive after spreading to other organs.
Because metastasis is responsible for most deaths from pancreatic cancer, any treatment that slows or prevents this process could have a major impact on patient outcomes.
Scientists are especially interested in exploring whether existing PCSK9-targeting drugs, currently used for cholesterol management, might eventually play a role in cancer treatment.
The research also highlights the growing understanding that cancer cells do not act alone. Instead, they constantly interact with their surrounding environment. Factors such as nutrient availability, oxygen levels, immune responses, and cholesterol metabolism can influence whether cancer cells survive or die after reaching a new organ.
Although the findings are promising, the research is still at an early stage. More studies will be needed to determine whether manipulating PCSK9 can safely and effectively help patients with pancreatic cancer. Clinical trials in humans will be necessary before any new treatment becomes available.
Even so, experts consider this discovery an important step forward in understanding one of the most aggressive and difficult-to-treat cancers. By uncovering how a single protein helps guide the spread of pancreatic cancer, scientists have opened a new avenue for research and potential therapy.
The study was supported by the National Institutes of Health, the National Science Foundation, and the American Association for Cancer Research. As researchers continue exploring the role of PCSK9 in cancer biology, the findings offer new hope that future treatments may be able to stop metastatic cancer before it takes hold in vital organs.
If you care about cancer, please read studies that low-carb diet could increase overall cancer risk, and new way to increase the longevity of cancer survivors.
For more health information, please see recent studies about how to fight cancer with these anti-cancer superfoods, and results showing daily vitamin D3 supplementation may reduce cancer death risk.
The research findings were published in the journal Nature.
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