Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis Academic Article Article uri icon

Overview

MeSH Major

  • Hemoperfusion
  • Kidney Diseases
  • Liver Diseases
  • Renal Dialysis

abstract

  • © 2019, The Author(s), under exclusive licence to Springer Nature Limited. The development of effective therapies against brain metastasis is currently hindered by limitations in our understanding of the molecular mechanisms driving it. Here we define the contributions of tumour-secreted exosomes to brain metastatic colonization and demonstrate that pre-conditioning the brain microenvironment with exosomes from brain metastatic cells enhances cancer cell outgrowth. Proteomic analysis identified cell migration-inducing and hyaluronan-binding protein (CEMIP) as elevated in exosomes from brain metastatic but not lung or bone metastatic cells. CEMIP depletion in tumour cells impaired brain metastasis, disrupting invasion and tumour cell association with the brain vasculature, phenotypes rescued by pre-conditioning the brain microenvironment with CEMIP+ exosomes. Moreover, uptake of CEMIP+ exosomes by brain endothelial and microglial cells induced endothelial cell branching and inflammation in the perivascular niche by upregulating the pro-inflammatory cytokines encoded by Ptgs2, Tnf and Ccl/Cxcl, known to promote brain vascular remodelling and metastasis. CEMIP was elevated in tumour tissues and exosomes from patients with brain metastasis and predicted brain metastasis progression and patient survival. Collectively, our findings suggest that targeting exosomal CEMIP could constitute a future avenue for the prevention and treatment of brain metastasis.

authors

publication date

  • November 2019

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1038/s41556-019-0404-4

PubMed ID

  • 31685984

Additional Document Info

start page

  • 1403

end page

  • 1412

volume

  • 21

number

  • 11