Why is one cell type in the pancreas more susceptible to tumor development than another?
Patients with pancreatic cancer still die too often of their disease. Improved knowledge on the mechanisms that are at the basis of the initiation of pancreatic cancer is crucial to allow for its early detection and to develop novel therapies. The cells that are responsible for the production and transport of the digestive juices are often at the basis of the formation of pancreas cancer. Though, there is still a lack of knowledge on the exact mechanisms. The Laboratory for Medical and Molecular Oncology of Prof. Ilse Rooman at the Vrije Universiteit Brussel conducts pioneering research in this domain.
Pancreatic acinar cells, that produce the digestive enzymes, are very sensitive to cellular stress such as during pancreatitis (an inflammatory condition). Thereby, they lose their own characteristics and acquire characteristics of duct cells, i.e. cells that take care of the transport of the digestive juices towards the small intestine. This disguise or dedifferentiation of acinar cells makes them more vulnerable and is predisposing for tumor formation. However, it still remains unclear to what extent dedifferentiated acinar cells differ from native duct cells, and which genes are uniquely regulating acinar cell dedifferentiation.
Using exocrine cell preparations from human donor material, Elyne Backx, a PhD student in Rooman’s group, analyzed for the first time the transcriptional profile of dedifferentiated acinar cells and native duct cells to find out why they are so different in susceptibility to neoplastic transformation. They discovered that in both cell types there were cancer pathways but involving different genes. The transcription factor MECOM was unique for the dedifferentiated acinar cells. It protected acinar cells from dying in an experimental pancreatitis setting, allowing them to stay on for tumor development. Moreover, MECOM was activated in this context by SOX9, which is indispensable for pancreatic tumor formation.
Recently, these findings were published in Cell Death and Differentiation, bringing us one step closer to understanding the early decision makers in the susceptibility of pancreatic cells to be at origin of cancer. The entire study is available at https://rdcu.be/chnob