Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver Academic Article uri icon

Overview

MeSH Major

  • Carcinoma, Pancreatic Ductal
  • Exosomes
  • Liver Neoplasms
  • Macrophage Migration-Inhibitory Factors
  • Pancreatic Neoplasms

abstract

  • Pancreatic ductal adenocarcinomas (PDACs) are highly metastatic with poor prognosis, mainly due to delayed detection. We hypothesized that intercellular communication is critical for metastatic progression. Here, we show that PDAC-derived exosomes induce liver pre-metastatic niche formation in naive mice and consequently increase liver metastatic burden. Uptake of PDAC-derived exosomes by Kupffer cells caused transforming growth factor β secretion and upregulation of fibronectin production by hepatic stellate cells. This fibrotic microenvironment enhanced recruitment of bone marrow-derived macrophages. We found that macrophage migration inhibitory factor (MIF) was highly expressed in PDAC-derived exosomes, and its blockade prevented liver pre-metastatic niche formation and metastasis. Compared with patients whose pancreatic tumours did not progress, MIF was markedly higher in exosomes from stage I PDAC patients who later developed liver metastasis. These findings suggest that exosomal MIF primes the liver for metastasis and may be a prognostic marker for the development of PDAC liver metastasis.

authors

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/ncb3169

PubMed ID

  • 25985394

Additional Document Info

start page

  • 816

end page

  • 26

volume

  • 17

number

  • 6