Mechanism of epithelial-mesenchymal transition of pancreatic cancer induced by pancreatic stellate cell

Abstract

Objective To explore the potential mechanism of epithelial-mesenchymal transition (EMT) of pancreatic cancer induced by pancreatic stellate cell (PSC). Methods The effect of PSC on EMT of pancreatic cancer was determined by direct co-culture. We also added signal pathway inhibitors and Notch-3 small interfere RNA (siRNA) to the co-culture system. Morphological change observation, two-chamber migration assays to assess the cell migration, fluorescent immunohistochemistry, Reverse transcriptase PCR (RT-PCR) and Western blotting to assess the expression level of Notch-3, E-cadherin, Vimentin was performed to determine whether the EMT happened. Results After co-culture with PSC, EMT phenomenon of PANC-1 happened with increased motility [mono-culture vs. co-culture, (16.4±2.6)/HP vs. (51.6±4.5)/HP, P=0.001]. L1790 (5 μmol/L, Notch signaling pathway inhibitor) can significantly inhibit the increased motility of PANC-1 cells, and suppress the occurrence of EMT. Notch-3 siRNA successfully inhibited Notch-3 gene expression, blocked the increased migration ability and EMT phenomenon of PANC-1 induced by PSC. Conclusion Notch-3 plays critical role in EMT of PANC-1 induced by PSC. Key words: Pancreatic cancer; Pancreatic stellate cell; Epithelial-mesenchymal transition