Cdc42-dependent transfer of mir301 from breast cancer-derived extracellular vesicles regulates the matrix modulating ability of astrocytes at the blood–brain barrier

Golnaz Morad, Cassandra C. Daisy, Hasan H. Otu, Towia A. Libermann, Simon T. Dillon, Marsha A. Moses

Research output: Contribution to journalArticle

Abstract

Breast cancer brain metastasis is a major clinical challenge and is associated with a dismal prognosis. Understanding the mechanisms underlying the early stages of brain metastasis can provide opportunities to develop efficient diagnostics and therapeutics for this significant clinical challenge. We have previously reported that breast cancer-derived extracellular vesicles (EVs) breach the blood–brain barrier (BBB) via transcytosis and can promote brain metastasis. Here, we elucidate the functional consequences of EV transport across the BBB. We demonstrate that brain metastasis-promoting EVs can be internalized by astrocytes and modulate the behavior of these cells to promote extracellular matrix remodeling in vivo. We have identified protein and miRNA signatures in these EVs that can lead to the interaction of EVs with astrocytes and, as such, have the potential to serve as targets for development of diagnostics and therapeutics for early detection and therapeutic intervention in breast cancer brain metastasis.

Original languageEnglish (US)
Article number3851
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
StatePublished - Jun 1 2020

Keywords

  • Blood
  • Brain barrier
  • Brain metastasis
  • Breast cancer
  • Extracellular vesicles
  • MicroRNA

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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