Evidence for Epithelial-Mesenchymal Transition in Adult Human Pancreatic Exocrine Cells

Abstract

It has been shown that adult pancreatic ductal cells can dedifferentiate and act as pancreatic progenitors. Dedifferentiation of epithelial cells is often associated with the epithelial-mesenchymal transition (EMT). In this study, we investigated the occurrence of EMT in adult human exocrine pancreatic cells both in vitro and in vivo. Cells of exocrine fraction isolated from the pancreas of brain-dead donors were first cultured in suspension for eight days. This led to the formation of spheroids, composed of a principal population of cells with duct-like phenotype. When cultivated in tissue culture-treated flasks, spheroid cells exhibited a proliferative capacity and coexpressed epithelial (cytokeratin7 and cytokeratin19) and mesenchymal (vimentin and alpha-smooth muscle actin) markers as well as marker of progenitor pancreatic cells (pancreatic duodenal homeobox factor-1) and surface markers of mesenchymal stem cells. The switch from E-cadherin to N-cadherin associated with Snail1 expression suggested that these cells underwent EMT. In addition, we showed coexpression of epithelial and mesenchymal markers in ductal cells of one normal adult pancreas and three type 2 diabetic pancreases. Some of the vimentin-positive cells were found to coexpress glucagon or amylase. These results point to the occurrence of EMT, which may take place on dedifferentiation of ductal cells during the regeneration or renewal of human pancreatic tissues.

Transforming growth factor‐β induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells

“…On the 5th day of culture, more than 80% of the cells were comprised duct cells with a small number of insulinproducing cells and fibroblasts. This result is consistent with recent study, which described that cell population after 8 days culture of human adult exocrine pancreatic cells consisted of ductal cells (75-82%), acinar cells (12-19%), and a few endocrine cells (3.5%) [Fanjul et al, 2010]. Thus, those cells were considered appropriate for the evaluation of the effects of TGF-b1 and had appropriate purity.…”

“…Our results are different from those of Seeberger et al [2009], who demonstrated EMT is an artifact of cell culture within human pancreas. But many other studies confirmed possibilities of EMT in human pancreatic epithelial cells in vitro and in vivo conditions [Dalvi et al, 2009;Fanjul et al, 2010]. So further researches are required to confirm the controversial results.…”

Transforming growth factor-beta1 induces microvascular abnormalities through a down-modulation of neural cell adhesion molecule in human hepatocellular carcinoma

“…51 In addition, it remains to be clarified if NCAM expression can be closely associated with a down-modulation of CD105 and if this could be considered another important step to predict epithelial to mesenchymal transition. 52,53 However, our data indirectly support this hypothesis, because nNL-StCs, which are less affected by their proximity to cancer cells than HCCStCs counterpart, possessed a higher basal level of CD105 and NCAM expression.…”

Radiofrequency pancreatic ablation and section of the main pancreatic duct does not lead to necrotizing pancreatitis

“…According to previous studies [17][18][19] to determine the apoptotic response and the ductal proliferation of the pancreas, cleaved-caspase 3 (as an apoptosis marker) and cytokeratin 7 (as a duct cell marker) were analyzed in the most representative samples.…”