Journal of Neuro-Oncology

, Volume 135, Issue 1, pp 37–46 | Cite as

CD133 positive U87 glioblastoma cells-derived exosomal microRNAs in hypoxia- versus normoxia-microenviroment

Laboratory Investigation

Abstract

Hypoxia is a major regulator of glioma development and aggressiveness. However, how CD133 positive U87 glioblastoma cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Communication with host cells and stroma via exosomes represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. MicroRNAs are thought to be essential actors of tumorigenesis as they are able to control the expression of numerous genes. Here, we show that exosomes derived from CD133+ U87 glioblastoma cells grown at hypoxic compared with normoxic conditions are potent proliferation inducers of the tumor vasculature and glioma cells proliferation in vitro. Moreover, we analyze the microRNA content of exosomes produced in vitro by hypoxia and normoxia CD133+ U87 glioblastoma cells using Affymetrix microarrays. It appears that the exosome microRNA profiles are qualitatively quite similar. Nevertheless, their quantitative profiles are different and may be potentially taken as an opportunity to carry out assays of diagnostic interest. We conclude that CD133+ U87 glioblastoma cells derived exosome-mediated miRNA transduction play an important role of mediating a proangiogenic response and glioma cells proliferation, and that the exosomal pathway constitutes a potentially targetable driver of hypoxia-dependent intercellular signaling during tumor development.

Keywords

Exosome Glioblastoma Hypoxia Normoxia MicroRNA 

Notes

Acknowledgements

This study was supported by grants from the Beijing Tiantan Hospital “Nursery Project” Foundation (No. 2014MP09), the National Natural Science Foundation of China (Nos. 81372354, 81302186), the Beijing Municipal Natural Science Foundation (No. 7151002), the Beijing Health System High-level Personnel Building Foundation (No. 2013-3-018), the Beijing Laboratory of Biomedical Materials Foundation (PXM2014_014226_000005) and the Beijing Municipal Administration of Hospitals’ Youth Program (No. QML20150505). We would like to thank Prof. Yilin Sun and Cuiping Zhang (Pathological Department, Beijing Neurosurgical Institute) for observing exosomes by transmission electron microscopy.

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest were disclosed.

Supplementary material

11060_2017_2566_MOESM1_ESM.doc (340 kb)
Supplementary material 1 (DOC 340 KB)
11060_2017_2566_MOESM2_ESM.doc (32 kb)
Supplementary material 2 (DOC 32 KB)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases (NCRC-ND), Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Brain Tumor, Beijing Tiantan HospitalCapital Medical UniversityBeijingPeople’s Republic of China
  2. 2.Department of Neurosurgery, Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan HospitalCapital Medical UniversityBeijingPeople’s Republic of China

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