MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer

Jakub Godlewski; Ruben Ferrer-Luna; Arun K Rooj; Marco Mineo; Franz Ricklefs; Yuji S Takeda; M Oskar Nowicki; Elżbieta Salińska; Ichiro Nakano; Hakho Lee; Ralph Weissleder; Rameen Beroukhim; E Antonio Chiocca; Agnieszka Bronisz

doi:10.1016/j.stemcr.2017.04.024

MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer

Stem Cell Reports. 2017 Jun 6;8(6):1497-1505. doi: 10.1016/j.stemcr.2017.04.024. Epub 2017 May 18.

Authors

Affiliations

¹ Department of Neurosurgery, Harvey Cushing Neuro-oncology Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].
² Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Cancer Program, BROAD Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Department of Neurosurgery, Harvey Cushing Neuro-oncology Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁴ Department of Neurosurgery, Harvey Cushing Neuro-oncology Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
⁵ Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences 02-106 Warsaw, Poland.
⁶ Department of Neurosurgery and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35243, USA.
⁷ Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁸ Department of Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁹ Department of Neurosurgery, Harvey Cushing Neuro-oncology Laboratories, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].

Abstract

Despite the importance of molecular subtype classification of glioblastoma (GBM), the extent of extracellular vesicle (EV)-driven molecular and phenotypic reprogramming remains poorly understood. To reveal complex subpopulation dynamics within the heterogeneous intratumoral ecosystem, we characterized microRNA expression and secretion in phenotypically diverse subpopulations of patient-derived GBM stem-like cells (GSCs). As EVs and microRNAs convey information that rearranges the molecular landscape in a cell type-specific manner, we argue that intratumoral exchange of microRNA augments the heterogeneity of GSC that is reflected in highly heterogeneous profile of microRNA expression in GBM subtypes.

Keywords: GBM; cancer heterogeneity; cancer stem cells; exosomes; extracellular vesicles; glioblastoma; microRNA; subtypes.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

AC133 Antigen / metabolism
Animals
Brain Neoplasms / genetics
Brain Neoplasms / pathology*
Exosomes / metabolism
Extracellular Vesicles / metabolism*
Female
Glioblastoma / genetics
Glioblastoma / pathology*
Humans
Mice
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism*
Neoplasm Invasiveness
Neoplastic Stem Cells / cytology
Neoplastic Stem Cells / metabolism
Phenotype
Tetraspanin 30 / metabolism
Transcriptome
Transplantation, Heterologous
Tumor Cells, Cultured

Substances

AC133 Antigen
MicroRNAs
PROM1 protein, human
Tetraspanin 30

Abstract

Publication types

MeSH terms

Substances

Grants and funding