Pancreatic cancers ‘talk’ to neighbouring cells in mice, pointing to potential new drug targets

In collaboration with the Press Association
Pancreatic cancer cells. Image credit: LRI EM Unit

Scientists have found a new way in which cells that surround pancreatic cancers in mice can help the tumours grow.

Pancreatic cancers can ‘talk’ to their neighbouring cells, which helps to protect the cancer cells and encourage them to grow and divide.

By listening in on this cellular chatter in mice, US scientists found a new signal called LIF that neighbouring cells relay to the cancer cells, encouraging them to grow. While the research, published in the journal Nature, is still at an early stage, scientists believe the discovery could open the door to studies into potential new treatments.

Dr Claus Jorgensen, a Cancer Research UK-funded pancreatic cancer expert, said: “The interplay between the tumour and the cells that surround it is already well known, but this study provides new and interesting insights into the signals and the effect they might have on tumours.”

Waking up the neighbours

Conversations between tumour cells and their neighbours isn’t a new concept. And scientists have homed in on a particular cellular culprit in the pancreas, called a pancreatic stellate cell.

These cells are usually dormant, but when activated can produce signals that form a protective shell around the tumour.

To understand more about the relationship between stellate cells and pancreatic tumours, scientists at the Salk Institute in California analysed the proteins that lab-grown stellate cells were releasing into their surroundings. One of the proteins that came up was LIF, or leukaemia inhibitor factor. 

"LIF is an important factor that normally helps stem cells maintain their developmental potential during the embryonic period, but usually vanishes in adulthood,” said Dr Yu Shi, a researcher at Salk and lead scientists on the study. “We found that activated stellate cells are secreting LIF, which acts on neighbouring cancer cells."

Changing the conversation

Salk’s Professor Tony Hunter said that previous studies have shown that killing pancreatic stellate cells can make tumours worse. 

"This means that you don't want to destroy the pancreatic stellate cells that secrete signalling factors, but rather want to stop them from delivering the stimulatory signals to the tumour cells."

Scientists found that blocking LIF in mice with molecules called antibodies slowed the growth of pancreatic cancers. It also boosted the effectiveness of chemotherapy in these early lab tests.

Jorgensen said that as always with studies like this, most of the data has come from mice and would need to be confirmed in people.

“Patients with this type of pancreatic cancer are typically treated with chemotherapy, but with limited effects. What’s particularly exciting about this study is the improved effect of combining anti-LIF antibodies with chemotherapy in mice,” he added.

The US team went on to check if LIF was found in samples from 77 people with pancreatic cancer. They found high levels of LIF in tumour samples and in patient’s blood.

And among 14 patients whose samples were tested after treatment, those whose samples had higher levels of LIF seemed to have a worse response to chemotherapy. 

References

Shi, Y et al. (2019) Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring. Nature. DOI: 10.1038/s41586-019-1130-6