Pancreatic stellate cells, which normally aid tissue repair, unwittingly help pancreatic cancer grow and spread in a method of 'cell hijack' only seen before in brain and breast cancer, according to new research from Queen Mary University of London.
The research, published in the latest issue of EMBO Molecular Medicine and carried out by Queen Mary's Barts Cancer Institute, also revealed the process can be blocked, thereby preventing the growth and spread of the tumour.
The study, funded by the UK charity Pancreatic Cancer Research Fund, set out to investigate the messaging mechanisms between cancer cells and the thick, fibrous stroma tissue that coats pancreatic tumours. It is this tissue which is believed to provide a nutrient-rich 'soil' in which cancer cells can grow.
Researchers found the cancer uses a protein called fibroblast growth factor receptor (FGFR) to hijack the stellate cells and force them to help the growth and spread of the tumour.
Ordinarily, FGF activates the stellate cells by binding to a receptor on the cell's surface. However, when examining donated human pancreatic cancer tissue, the researchers saw that FGFR had travelled directly to the nucleus, taking control and forcing the stellate cells to multiply and communicate with the cancer cells. This 'nuclear translocation' - which has only been seen in brain and breast cancer cells before - was most prominent in areas where the tumour was invading normal tissue.
Dr Stacey Coleman, lead author based at Queen Mary University of London, comments:
"We certainly weren't expecting to see this happening in pancreatic stellate cells but our results were emphatic. When we modelled what was happening and put activated stellate cells together with pancreatic cancer cells, the two-way signalling became more intense as the stellate cells and the cancer cells proliferated, in a vicious cycle of growth. When we blocked the FGFR activity and prevented the stellate cells from being hijacked, the cancer cells completely stopped growing and invading."
Pancreatic cancer often shows resistance to conventional chemotherapy, partly because the stroma prevents therapies reaching the tumour cells. The researchers believe these latest findings could pave the way for the development of a new combined therapy approach, able to both prevent the spread of cancer cells and weaken the stroma environment to allow chemotherapy to access the tumour.
Dr Stacey Coleman concludes:
"Our next steps are to investigate what changes occur when FGFR travels to the nucleus of stellate cells so we can find out how these cells may cause the stroma to develop and provide such a good environment for the cancer cells."
Maggie Blanks, CEO of the Pancreatic Cancer Research Fund, comments: "This is another example of the leading research we fund in the UK and I congratulate the Queen Mary team for their findings. Our research strategy is to enable the development of new treatments - whether alone or in combination with traditional therapies. These exciting findings suggest there's definitely something here that warrants further investigation that could prove significant for improving the treatment of pancreatic cancer."
Notes to the editor
Copies of the full paper are available on request.
About Queen Mary University of London
Queen Mary University of London is the "biggest star" among the UK's leading research-intensive higher education institutions, with five campuses in the capital: Mile End, Whitechapel, Charterhouse Square, West Smithfield and Lincoln's Inn Fields.
A member of the Russell Group, Queen Mary is also one of the largest of the colleges of the University of London, with 17,800 students - 20 per cent of whom are from more than 150 countries.
Some 4,000 staff deliver world-class degrees and research across 21 departments, within three Faculties: Science and Engineering; Humanities and Social Sciences; and the School of Medicine and Dentistry.
League table rankings
- 11th in the UK (Research Assessment Exercise, 2008), according to the Guardian
- 35th in the UK - Complete University Guide 2014
- 36th in the UK - Guardian University Guide 2014
- 114th globally and 14th in the UK - The Times Higher World University Rankings 2013-4
- 115th globally and 19th in the UK - 2013-4 QS World Rankings
- Top 30 in the UK and in the top 201-300 bracket globally - Shanghai Jiao Tong Academic Rankings of World Universities 2013
Queen Mary has an annual turnover of £350m, research income worth £100m, and generates employment and output worth £700m to the UK economy each year.
Unique for London universities, Queen Mary has an integrated residential campus in Mile End - a 2,000-bed award-winning Student Village overlooking the scenic Regents Canal.
PCRF is the only UK charity exclusively funding research into pancreatic cancer. The charity has so far funded 27 research projects worth some £4 million across UK universities and these projects are funded entirely from public donations.
About pancreatic cancer
Each year approximately 8,800 people in the UK are diagnosed with pancreatic cancer. It is an extremely difficult cancer to diagnose and treat because it is unusually aggressive, symptoms are often vague and generally appear at an advanced stage of the disease. Around three per cent of those diagnosed with pancreatic cancer will survive for five years or more, a figure that has barely improved in forty years.