Cells of origin of pancreatic cancer: Experimental animal tumors related to human pancreas

Human pancreatic adenocarcinoma is traditionally believed to be ductal in origin, primarily due to the presence of complexes of tubules interpreted as being derived from ductular proliferation. Although observations in various animal models of pancreatic tumors suggested that acinar cells were undergoing dedifferentiation to form tubular complexes, this process was difficult to reconcile with an acinar arrangement of the pancreas. Using three‐dimensional reconstructions and retrograde injections, it was concluded that the normal pancreas actually has a tubular arrangement. The tubules branch, curve, and anastomose. By losing zymogen granules and decreasing in height, acinar units become recognized as ductule‐like structures. Therefore, the presence of tubular complexes should not be taken to indicate that carcinogenesis has taken place or to eliminate acinar cells as possible cells of origin of adenocarcinoma, which by present criteria would be classified as ductal.