Double agent betrays pancreas

A star-shaped cell in the pancreas acts as a double agent – it helps the body respond to damage and disease, but also stimulates the growth of cancer and protects against radiotherapy.

A drug to sever specific communication lines between pancreatic cancer cells and stellate cells could improve patients’ response to radiotherapy in the future says Professor Thomas Brunner from the Gray Institute for Radiation Oncology and Biology at the University of Oxford.

Brunner has just published the first paper to demonstrate the influence of pancreatic stellate cells in how effective radiotherapy is in destroying cancer cells.  His research team looked at the survival of pancreatic cancer cells in the lab when dosed with radiation. They found that when co-cultured with noncancerous stellate cells, radiation was less effective at killing off the cancer cells.

In mouse models, tumour growth was faster with pancreatic stellate cells present, with the stellate cells providing a protective shield – reducing the effect of radiotherapy on the cancer.

“It turns out that stellate cells are partners in crime with cancer cells,” said Brunner. “They actively help the tumour cells and have a protective effect against radiotherapy.”

“While they normally help defend the pancreas against injury – wound healing is very critical – this response needs to stop at some point or it is harmful. In pancreatic cancer, this wound healing response becomes active forever and that’s counterproductive in the end.”

Researchers looked at a number of signalling pathways that might be responsible for this effect by allowing cancer cells and stellate cells to communicate. They believe integrins – molecules on the surface of the cells – are likely to be involved.

“Blocking the integrin signalling gets rid of any protective effects against radiotherapy,” Brunner said. “By finding the mechanism behind this effect, we ultimately may be able to develop a drug to target this process and improve the outcome of radiotherapy.”