Epithelial-To-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fiction or Fact?

Nicoletta Gagliano*

Epithelial-To-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fiction or Fact.

Despite continuous progress in imaging, surgical techniques, intensive care, and chemotherapeutic approaches, the current overall 5-year survival is less than 6%.

In carcinoma progression, including PDAC, cancer cells acquire their metastatic phenotype undergoing a complex step-wise process defined as Epithelial-To-Mesenchymal Transition, leading to a “phenotypic switch” of epithelial cells to mesenchymal cells.

The epithelial phenotype is characterized by distinct, well demarcated intercellular adhesive structures, and
apical-basal polarity, all mediated by the expression of E-cadherin on the plasma membrane of the cell.

The EMT-related phenotype of carcinoma cells is characterized
by the loss of epithelial features, including loss of cell adhesion and polarity, down-regulation
of E-cadherin, cytoskeleton reorganization by expressing vimentin and α-Smooth Muscle Actin. Moreover,
the acquisition of motile properties and secretion of Matrix Metalloproteinases leads to the disruption of basement membranes.

The key event of EMT is considered the loss of E-cadherin, a transmembrane glycoprotein with its intracellular domain linked to β-catenin to form the E-cadherin/β-catenin complex, mediating cell-cell adhesion and playing a major role in the control of epithelial cell
architecture, differentiation and phenotype.

Interestingly, the EMT process can exhibit different characteristics in
different carcinoma cells, therefore sometimes is difficult to recognize the typical EMT-related phenotype
and the events responsible of carcinoma progression.

This is evident in PDAC, since it was
shown that 6 out of 7 PDAC cell lines maintain E-cadherin expression on the cell membrane,
and that the expression of some EMT markers in PDAC are similar than in benign pancreatic ducts.

Pancreas Open J. 2015; 1(1): e1-e4. doi: 10.17140/POJ-1-e001