Exosomes derived from pancreatic stellate cells

Tetsuya Takikawa, Atsushi Masamune, Naoki Yoshida, Shin Hamada, Takayuki Kogure, Toru Shimosegawa

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objectives Pancreatic stellate cells (PSCs) interact with pancreatic cancer cells in the tumor microenvironment. Cell constituents including microRNAs may be exported from cells within membranous nanovesicles termed exosomes. Exosomes might play a pivotal role in intercellular communication. This study aimed to clarify the microRNA signature of PSC-derived exosomes and their effects on pancreatic cancer cells. Methods Exosomes were prepared from the conditioned medium of immortalized human PSCs. MicroRNAs were prepared from the exosomes and their source PSCs, and the microRNA expression profiles were compared by microarray. The effects of PSC-derived exosomes on proliferation, migration, and the mRNA expression profiles were examined in pancreatic cancer cells. Results Pancreatic stellate cell-derived exosomes contained a variety of microRNAs including miR-21-5p. Several microRNAs such as miR-451a were enriched in exosomes compared to their source PSCs. Pancreatic stellate cell-derived exosomes stimulated the proliferation, migration and expression of mRNAs for chemokine (C - X - C motif) ligands 1 and 2 in pancreatic cancer cells. The stimulation of proliferation, migration, and chemokine gene expression by the conditioned medium of PSCs was suppressed by GW4869, an exosome inhibitor. Conclusions We clarified the microRNA expression profile in PSC-derived exosomes. Pancreatic stellate cell-derived exosomes might play a role in the interactions between PSCs and pancreatic cancer cells.

Original languageEnglish
Pages (from-to)19-27
Number of pages9
JournalPancreas
Volume46
Issue number1
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • BrdU - 5 - bromo - 2 - deoxyuridine
  • CCL20 - chemokine (C - C motif) ligand 20
  • CM - conditioned medium
  • CXCL - chemokine (C - X - C motif) ligand
  • DMEM - Dulbecco's Modified Eagle Medium
  • FBS - fetal bovine serum
  • IPA - ingenuity pathway analysis
  • Key Words/Abbreviations chemokine
  • OD - optical density
  • PSC - pancreatic stellate cell
  • fibrosis
  • microarray
  • myofibroblast
  • stroma

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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