Pancreatic cancer is one of the hardest cancers to treat because it is often discovered only after it has begun to spread.
The most common form, pancreatic ductal adenocarcinoma, or PDAC, accounts for the great majority of pancreatic cancer cases and has a very low long-term survival rate.
The pancreas sits behind the stomach and helps the body digest food and control blood sugar. Cancer can grow in this organ for some time without causing clear symptoms, which is one reason early diagnosis is so difficult.
Researchers at the Francis Crick Institute have identified a protein that may help explain why some pancreatic cancer cells are especially good at growing and forming new tumors. The discovery could eventually provide scientists with another target for future treatments.
The team, led by Axel Behrens, focused on a small group of cells inside pancreatic tumors known as cancer stem cells. These cells have some abilities similar to normal stem cells, including the ability to produce new cells.
In a tumor, however, this ability can be dangerous. Cancer stem cells can help maintain tumor growth and may contribute to the cancer spreading or returning after treatment.
The researchers studied which genes were active in these cells and identified a protein called CD9 on their surface. CD9 appeared in cancer stem cells in both early and more developed pancreatic tumors.
This made CD9 useful as a way of identifying the tumor-forming cells, but the researchers discovered that it was doing more than simply marking them. The protein itself appeared to help the cancer become more aggressive.
In experiments with mice, reducing CD9 activity led to smaller tumors. When researchers increased CD9 levels, the cancer cells formed larger and faster-growing tumors, suggesting that the protein actively supports tumor growth.
The team also examined information from people with pancreatic cancer. Patients whose tumors contained particularly high levels of CD9 tended to have poorer outcomes, and the researchers estimated that this high-CD9 group represented roughly 10% of patients studied.
The next question was why CD9 made such a difference. The answer appeared to involve glutamine, an amino acid that cells can use as a source of nutrients and as raw material for making other molecules needed for growth.
Cancer cells have unusually high demands for energy and building materials because they divide rapidly. The researchers found that CD9 helped pancreatic cancer stem cells take in more glutamine, effectively giving these aggressive cells greater access to an important source of fuel.
When CD9 was present at high levels, the cancer cells absorbed more glutamine and were better able to grow. This connection between a surface protein and the way cancer cells obtain nutrients revealed a possible weakness that researchers may be able to exploit.
One future strategy could be to interfere with CD9 or the processes it controls. If scientists can safely reduce the ability of cancer stem cells to obtain the nutrients they need, it may become possible to slow tumor growth or make the cancer more vulnerable to other treatments.
However, the research does not yet provide a new treatment for patients. Much more work is needed to determine whether CD9 can be targeted safely in humans and whether blocking it would produce meaningful benefits without harming healthy cells.
Pancreatic cancer remains difficult to treat, and current care can include surgery, chemotherapy, radiation and newer combinations of medicines depending on the stage of disease. Finding biological features that distinguish the most dangerous tumor cells could help researchers develop more precise therapies in the future.
The study from the Francis Crick Institute and collaborators was published in the journal Nature Cell Biology. By showing how CD9 helps pancreatic cancer stem cells obtain glutamine and drive tumor growth, the research offers a new clue about how one of the deadliest cancers survives and spreads.
If you care about cancer, please read studies that artificial sweeteners are linked to higher cancer risk, and how drinking milk affects risks of heart disease and cancer.
For more health information, please see recent studies about the best time to take vitamins to prevent heart disease, and results showing vitamin D supplements strongly reduces cancer death.
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