IL-6/STAT3 Plays a Regulatory Role in the Interaction Between Pancreatic Stellate Cells and Cancer Cells

Shin Hamada, Atsushi Masamune, Naoki Yoshida, Tetsuya Takikawa, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

Background: Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis, a characteristic feature of pancreatic cancer. Although it is still controversial, previous studies have suggested that PSCs promote the progression of pancreatic cancer by regulating the cell functions of cancer cells. PSCs produce large amounts of IL-6, which promotes the accumulation of myeloid-derived suppressor cells via a signal transducers and activator of transcription 3 (STAT3)-dependent mechanism. But the role of IL-6/STAT3 pathway in the interaction between PSCs and pancreatic cancer cells remains largely unknown. Aims: To clarify the role of IL-6/STAT3 in the interaction between PSCs and cancer cells. Methods: Human pancreatic cancer cells (Panc-1 and SUIT-2 cells) were treated with conditioned medium of immortalized human PSCs (PSC-CM). The effects of PSC-CM and IL-6 neutralization on the mRNA expression profiles were examined using Agilent’s microarray. Activation of STAT3 was assessed by Western blotting using an anti-phospho-specific antibody. Cellular migration was examined by a two-chamber assay. The expression of markers related to epithelial–mesenchymal transition (EMT) was assessed by real-time reverse transcription PCR. Results: PSC-CM induced the activation of STAT3 in pancreatic cancer cells. Neutralization of IL-6 suppressed the PSC-CM-induced upregulation of genes including complement factor B, lipocalin, and chemokine (C–C motif) ligand 20. Inhibition of IL-6/STAT3 pathway by anti-IL-6 antibody or a STAT3 inhibitor (NSC74859) inhibited the PSC-CM-induced migration and the expression of EMT-related markers (Snail and cadherin-2) in pancreatic cancer cells. Conclusion: IL-6/STAT3 pathway regulates the PSC-induced EMT and alterations in gene expression in pancreatic cancer cells.

Original languageEnglish
Pages (from-to)1561-1571
Number of pages11
JournalDigestive Diseases and Sciences
Volume61
Issue number6
DOIs
Publication statusPublished - 2016 Jun 1

Keywords

  • Desmoplastic reaction
  • Epithelial–mesenchymal transition
  • Fibrosis
  • Pancreatic cancer
  • Pancreatitis
  • Stroma

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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