The epithelial to mesenchymal transition in pancreatic cancer: A systematic review.

BACKGROUND/OBJECTIVES: The present article summarizes and analyzes the current knowledge about the role of the epithelial to mesenchymal transition (EMT) in the systemic invasiveness of pancreatic cancer.

METHOD: An electronic search of PubMed/MEDLINE, EMBASE, and the Web of Science was used to identify relevant original articles and reviews.

RESULTS: The EMT represents a key step during normal embryogenesis. However, increasing evidence reveals its essential role in the local progression and metastasis of pancreatic cancer. Areas of interest are the cross-linking between cells undergoing the EMT and pancreatic cancer stem cells, and the correlation between the EMT and chemoresistance to standard therapies. During carcinogenesis, malignant pancreatic cells at the primary site acquire the ability to undergo the EMT, a transformation associated with increased mobility. The reverse process at secondary sites, the mesenchymal to epithelial transition (MET), has devastating consequences, allowing neoplastic epithelial cells to invade surrounding tissues and spread to distant sites. Consequences of the EMT are the loss of E-cadherin expression and the acquisition of mesenchymal markers including fibronectin or vimentin. Detailed knowledge of the molecular processes underlying the EMT has opened possibilities for new therapeutic agents. These include an EMT approach for patients with early cancers, to prevent invasion and dissemination, and anti-MET therapy for patients with established metastasis.

CONCLUSIONS: The current literature shows a strong correlation between the EMT and the systemic aggressiveness of pancreatic tumors. Individualized therapy, targeting the process of EMT and its cross-linking with cancer stem cells, may increase survival of patients with pancreatic cancer.