Exosomes derived from pancreatic cancer cells induce activation and profibrogenic activities in pancreatic stellate cells

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

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes. PCC-derived exosomes stimulated the proliferation, migration, activation of ERK and Akt, the mRNA expression of α-smooth muscle actin (ACTA2) and fibrosis-related genes, and procollagen type I C-peptide production in PSCs. Ingenuity pathway analysis of the microarray data identified transforming growth factor β1 and tumor necrosis factor as top upstream regulators. PCCs increased the expression of miR-1246 and miR-1290, abundantly contained in PCC-derived exosomes, in PSCs. Overexpression of miR-1290 induced the expression of ACTA2 and fibrosis-related genes in PSCs. In conclusion, PCC-derived exosomes stimulate activation and profibrogenic activities in PSCs. Exosome-mediated interactions between PSCs and PCCs might play a role in the development of the tumor microenvironment.

Original languageEnglish
Pages (from-to)71-77
Number of pages7
JournalBiochemical and biophysical research communications
Volume495
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

Keywords

  • Fibrosis
  • Myofibroblast
  • Pancreatitis
  • Stroma
  • Tumor microenvironment
  • microRNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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