Mechanism controlling spread of pancreatic cancer discovered by scientists

Scientists have shown it is possible to reverse a key process that allows pancreatic cancer cells to grow and spread around the body.

These findings, published in Nature, show that a protein called GREM1 is key to regulating the type of cells found in pancreatic cancer – and manipulating its levels can both fuel and reverse the ability of these cells to change into a more aggressive subtype.

The researchers believe this fundamental discovery could ultimately pave the way for new pancreatic cancer treatments.

Switching off GREM1 caused the tumour 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 tumour 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 percent of mice without functioning, GREM1 developed tumours that had spread to their liver, compared to 15 percent of mice where GREM1 was working normally.

The scientists showed that boosting GREM1 levels could reverse this process and cause invasive cell types to revert into a less dangerous form.

The researchers, who work in the Breast Cancer Now Toby Robins Research Centre at the ICR, stress that the science is early stage, and significant amounts of research would be required to discover and develop treatments that change PDAC cell fates and make the tumour respond better to therapies. However, fundamental discoveries such as this are crucial in directing efforts to find new cancer drugs and treatments.

The researchers also discovered that another protein, called 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 – from the patterns on the skin of the giant puffer fish to seashells – and strikingly the same sort of patterns are seen 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.

Reference:

Lan, L., Evan, T., Li, H. et al. GREM1 is required to maintain cellular heterogeneity in pancreatic cancer. Nature (2022). https://doi.org/10.1038/s41586-022-04888-7.