Discovery of CAFs’ origin gives new direction for pancreatic cancer
US researchers discovered a type of cell involved it pancreatic cancer and sheds light on the origin of cancer-associated fibroblasts (CAFs).
New research from the Medical University of South Carolina (MUSC), US, showed that a type of cell that plays a key role in pancreatic cancer can trace its origin back to a structure that forms during embryonic development.
This new data, published in Nature Communications, is the first to show the cellular origin of normal pancreatic fibroblasts and cancer-associated fibroblasts (CAFs) that influence tumour progression. The findings open the door for new therapeutic targets for pancreatic cancer, which remains challenging to treat.
“We are still learning about the cells that make up the tumour microenvironment. New therapies often take decades to develop because we first must understand tumour biology. Our recent discovery about the origin of cancer-associated fibroblasts will help the pancreatic cancer field to progress,” said Dr Michael Ostrowski, the WH Folk Endowed Professor in Experimental Oncology.
While pancreatic cancer is driven by tumour cells, fibroblasts are cells that control the microenvironment around the tumour. “A healthy pancreas contains very few fibroblasts. However, there is a drastic increase in the number of fibroblasts when a tumour forms in the pancreas and fibroblasts play important and complex roles in how the disease progresses,” Dr Lu Han added, lead author of the study.
The potential CAF origins include pancreatic epithelial cells, the bone marrow and pancreatic resident fibroblasts – fibroblasts in the normal adult pancreas. They formally tested that hypothesis by engineering elegant mouse genetic models of pancreatic cancer.
“What we found was a bit surprising. The bone marrow and epithelial cells only had minimal contributions to CAFs. We found that both resident fibroblasts and CAFs came from the splanchnic mesenchyme, a layer of cells in an embryo during early development,” Han said.
This new finding about the foetal origin of the pancreatic fibroblasts suggested that the different CAF subtypes found in pancreatic cancer are likely caused by the tumour microenvironment driving the diversification of the fibroblasts.