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. The research also revealed that the process can be blocked, thereby preventing the growth and spread of the tumor.
The study set out to investigate the messaging mechanisms between cancer cells and the thick, fibrous stroma tissue that coats pancreatic tumors. It is this tissue which is believed to provide a nutrient-rich ‘soil’ in which cancer cells can grow.
Researchers found that 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 tumor.
Ordinarily, FGFR 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 until now, was most prominent in areas where the tumor was invading normal tissue.
“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,” said lead author Stacey Coleman, PhD, of Queen Mary University of London in the United Kingdom. The study was published in EMBO Molecular Medicine (2014; doi:10.1002/emmm.201302698).
Pancreatic cancer often shows resistance to conventional chemotherapy, partly because the stroma prevents therapies reaching the tumor cells. The researchers believe that these latest findings could pave the way for the development of a new combined therapy approach that could be able to both prevent the spread of cancer cells and weaken the stroma environment to allow chemotherapy to access the tumor.
“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,” said Coleman.