Activation of pancreatic stellate cells involves an EMT-like process

Int J Oncol. 2016 Feb;48(2):783-92. doi: 10.3892/ijo.2015.3282. Epub 2015 Dec 8.

Abstract

Pancreatic adenocarcinoma (PDAC) and chronic pancreatitis (CP) are characterized by a desmoplastic reaction involving activated pancreatic stellate cells (PSCs). However, the mechanisms of PSC activation remain poorly understood. We examined whether the epithelial-mesenchymal transition (EMT) process might play a role in PSC activation. PSCs were isolated from a rat pancreas and characterized using immunofluorescence and immunocytochemistry. We evaluated changes in cell motility and in the expression levels of a panel of EMT-related genes during the PSC activation process. Activation of PSCs occurred after 48 h of in vitro culture, as indicated by a morphological change to a myofibroblastic shape and a decrease in the number of cytoplasmic lipid droplets. After activation, PSCs showed enhanced cell migration ability compared to quiescent cells. In addition, the expression of epithelial markers (E-cadherin, BMP7 and desmoplakin) decreased, while expression of mesenchymal markers (N-cadherin, vimentin, fibronectin1, collagen1α1 and S100A4) increased in activated PSCs. EMT-related transcription factors (Snail and Slug) were also upregulated after PSC activation. The concurrent increase in cell migration ability and alterations in EMT-related gene expression suggests that the activation of PSCs involves an EMT-like process. The knowledge that PSC activation involves an EMT‑like process may help to identify potential new therapeutic targets to alleviate pancreatic fibrosis in diseases like CP and PDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Biomarkers, Tumor / metabolism
  • Bone Morphogenetic Protein 7 / genetics
  • Cadherins / metabolism
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Desmoplakins / metabolism
  • Epithelial-Mesenchymal Transition / physiology*
  • Male
  • Pancreas / metabolism
  • Pancreas / pathology*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Stellate Cells / metabolism
  • Pancreatic Stellate Cells / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / metabolism
  • Up-Regulation / physiology

Substances

  • Biomarkers, Tumor
  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 7
  • Cadherins
  • Desmoplakins
  • Transcription Factors