GREM1 Controls Fate of Pancreatic Cancer Cells

Researchers in the U.K. have identified a protein that plays a role in pancreatic cancer cells turning into a more aggressive form and further shown that the process can be reversed. The findings pave the way for new treatments for the deadly cancer.

In a study published recently in Nature, a team from Institute of Cancer Research, London, reports that a protein called GREM1 is key to regulating the type of cells found in pancreatic cancer. Levels of the protein can also be manipulated to both fuel and reverse the ability of these cells to change into a more aggressive subtype.

The study used mice with pancreatic cancer with the gene that switches off the GREM1 protein and pancreatic organoids.

In the organoids, switching off GREM1 caused the tumor cells to rapidly change shape and develop new properties that help them invade new tissues and migrate around the body. Within just 10 days, all the tumor cells changed their identity into a dangerous, invasive cell type.

Switching off the gene also made tumors in mice more likely to spread. The researchers studied a mouse model of pancreatic ductal adenocarcinoma (PDAC), the most common and aggressive form of the disease. Around 90% of mice without functioning GREM1 developed tumors that had spread to their liver, compared to 15% of mice where GREM1 was working normally.

Crucially, the scientists then showed that boosting GREM1 levels could reverse this process and cause invasive cell types to revert into a less dangerous form. Researchers hope to use this knowledge to find ways to reverse more advanced pancreatic cancer into a less aggressive form, which is easier to treat.

“This is an important and fundamental discovery that opens up a new avenue for uncovering treatments for pancreatic cancer. We have shown that it is possible to reverse cell fate in pancreatic cancer in the lab—turning back the clock on aggressive tumors and switching them to a state that makes them easier to treat,” says Professor Axel Behrens, senior author of the study. “By better understanding what drives the aggressive spread of pancreatic cancer, we hope to now exploit this knowledge and identify ways to make pancreatic cancer less aggressive, and more treatable.”

The researchers also discovered that another protein, BMP2, is involved in regulating GREM1, and that these two proteins regulate the form PDAC cells ultimately take, according to a mathematical model first proposed by Alan Turing in 1952. These Turing patterns are found in nature and in the different types of cells found in pancreatic cancer. Further studies are needed to determine whether this model is also applicable in other forms of cancer.