Elsevier

Translational Oncology

Volume 6, Issue 6, December 2013, Pages 638-648, IN5-IN6
Translational Oncology

Ionizing Radiation and Glioblastoma Exosomes: Implications in Tumor Biology and Cell Migration1,2

https://doi.org/10.1593/tlo.13640Get rights and content
Under a Creative Commons license
open access

Abstract

Exosomes are nanometer-sized lipid vesicles released ubiquitously by cells, which have been shown to have a normal physiological role, as well as influence the tumor microenvironment and aid metastasis. Recent studies highlight the ability of exosomes to convey tumor-suppressive and oncogenic mRNAs, microRNAs, and proteins to a receiving cell, subsequently activating downstream signaling pathways and influencing cellular phenotype. Here, we show that radiation increases the abundance of exosomes released by glioblastoma cells and normal astrocytes. Exosomes derived from irradiated cells enhanced the migration of recipient cells, and their molecular profiling revealed an abundance of molecules related to signaling pathways important for cell migration. In particular, connective tissue growth factor (CTGF) mRNA and insulin-like growth factor binding protein 2 (IGFBP2) protein levels were elevated, and coculture of nonirradiated cells with exosomes isolated from irradiated cells increased CTGF protein expression in the recipient cells. Additionally, these exosomes enhanced the activation of neurotrophic tyrosine kinase receptor type 1 (TrkA), focal adhesion kinase, Paxillin, and proto-oncogene tyrosine-protein kinase Src (Src) in recipient cells, molecules involved in cell migration. Collectively, our data suggest that radiation influences exosome abundance, specifically alters their molecular composition, and on uptake, promotes a migratory phenotype.

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1

This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. No conflict of interest to disclose.

2

This article refers to supplementary materials, which are designated by Figures W1 to W3 and are available online at www.transonc.com