Scientists discover mechanism controlling spread of pancreatic cancer

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

Researchers from The Institute of Cancer Research, London, studied pancreatic cancer with the gene that makes the GREM1 protein switched off in mice, and in pancreatic ‘mini-tumours’, which are also known as organoids.

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 tumours 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 per cent of mice without functioning GREM1 developed tumours which had spread to their liver, compared to 15 per cent of mice where GREM1 was working normally.

Making advanced pancreatic cancer less aggressive

Crucially, the scientists, who were largely funded by The Institute of Cancer Research (ICR), which as well as being a research institute is also a charity, then showed that boosting GREM1 levels could reverse this process and cause invasive cell types to revert into a less dangerous form. Researchers hope, in the future, to use this knowledge to find ways to reverse more advanced pancreatic cancer into a less aggressive form, which is easier to treat.

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.