New insight on the mechanism of pancreatic tumorigenesis


Pancreatic cancer is currently one of the deadliest cancers. It can be initiated by two different types of initiating lesions. One of these is called intraductal papillary mucinous neoplasia(IPMN). IPMN is the only pancreatic cancer lesion that is currently detected by medical imaging. It shows an increase of 14 times in incidence between 1985 and 2005. IPMNs are benign cystic lesions, but they evolve into malignant lesions in about 20 to 40 % of cases. For this reason, there is a need to understand how IPMNs develop.

IPMN seems to originate from a pancreatic cell type called ductal cells. These ductal cells form a network of ducts that collect the enzymatic secretions produced by another pancreatic cell type, the acinar cells, to bring them to the intestine where they allow digestion of the alimentary bolus.

Histological section of the pancreas of a mouse developing IPMN. The arrows show IPMN-initiating lesions localized around a pancreatic duct.

In a study recently published in the journal Gut, a team of researchers led by Louis Collet, Elsa Ghurburrun, Ivan Borbath, and Patrick Jacquemin was interested in the cellular origin of IPMNs. By analyzing a novel mouse model they created, they found that IPMNs come from cells located in large pancreatic ducts and they identify an important signaling pathway for the development of IPMNs. Their results indicate that initiating lesions that cause pancreatic cancer have different cell origins and most likely evolve through different pathways. They show that in the future, determining this origin may influence the therapeutic strategy to be implemented when confronted with pancreatic cancer.

Louis Collet and Elsa Ghurburrun, the two PhD researchers who performed the study.

Article describing this research

Kras and LKB1 mutations synergistically induce intraductal papillary mucinous neoplasm derived from pancreatic duct cells.

Collet L, Ghurburrun E, Meyers N, Assi M, Pirlot B, Leclercq IA, Couvelard A, Komuta M, Cros J, Demetter P, Lemaigre FP, Borbath I, Jacquemin P.

Gut (2019) Jun 1. pii: gutjnl-2018-318059. doi: 10.1136/gutjnl-2018-318059.