Activation of pancreatic stellate cells involves an EMT-like process

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.

The Expression of E-Cadherin and Vimentin in Non-Small-Cell Lung Cancer and Their Correlation with Epithelial-Mesenchymal Transition (EMT)

“…Vlahov N et al [8] found the expression of E-cadherin lost mostly or partially in some malignant tumor deriving from epithelial tissues. The evidence showed that the E-cadherin lost or decreased in a range of tumors, such as breast cancer [3], lung cancer [9], pancreas cancer [10].…”

Galectin-1 expression in activated pancreatic satellite cells promotes fibrosis in chronic pancreatitis/pancreatic cancer via the TGF-β1/Smad pathway

“…Pancreatic fibrosis is closely associated with CP and pancreatic cancer (PC) and it induces severe damage in the pancreas. CP and PC are characterized by a desmoplastic reaction that involves activated pancreatic stellate cells (PSCs) (1)(2)(3). This reaction promotes the growth and invasion of tumor cells (3)(4)(5).…”

“…CP and PC are characterized by a desmoplastic reaction that involves activated pancreatic stellate cells (PSCs) (1)(2)(3). This reaction promotes the growth and invasion of tumor cells (3)(4)(5). The activation of PSCs has been previously proposed as the key initiating step in pancreatic fibrosis (6) and a major source of extracellular matrix (ECM) deposition during pancreatic injury (7).…”

Curcumin analogs: Their roles in pancreatic cancer growth and metastasis

“…A special characteristic property of the EMT pathway is the transition of epithelial E‐cadherin to mesenchymal N‐cadherin. PSCs in PC can promote the EMT pathway by reducing E‐cadherin expression and elevating vimentin and Snail1 expressions . Due to the lack of specific evidence and limited information regarding the specific mechanisms involved, it has been assumed that aberrant vascularity and augmented fibrosis due to PSC activation results in hypoxia, which can promote EMT transition in PC.…”

“…PSCs in PC can promote the EMT pathway by reducing E-cadherin expression and elevating vimentin and Snail1 expressions. [9][10][11] Due to the lack of specific evidence and limited information regarding the specific mechanisms involved, it has been assumed that aberrant vascularity and augmented fibrosis due to PSC activation results in hypoxia, which can promote EMT transition in PC. It has previously been demonstrated that activation of PSCs, increasing EMT and DNA methylation could be a potential therapeutic strategy in the treatment of PC.…”