Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier

Authors

Golnaz Morad, Boston Children’s Hospital & Harvard Medical School, BostonFollow
Cassandra C. Daisy, Boston Children’s HospitalFollow
Hasan H. Otu, University of Nebraska-LincolnFollow
Towia A. Libermann, Beth Israel Deaconess Medical Center, Boston & Harvard Medical SchoolFollow
Simon T. Dillon, Beth Israel Deaconess Medical Center, Boston & Harvard Medical SchoolFollow
Marsha A. Moses, Boston Children’s Hospital & Harvard Medical School, BostonFollow

Document Type

Article

Date of this Version

2020

Citation

Int. J. Mol. Sci. 2020, 21, 3851; doi:10.3390/ijms21113851

www.mdpi.com/journal/ijms

Comments

2020 by the authors.

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.