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Open Access 01-10-2016 | Laboratory Investigation

Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting

Authors: Sune Munthe, Mia D. Sørensen, Mads Thomassen, Mark Burton, Torben A. Kruse, Justin D. Lathia, Frantz Rom Poulsen, Bjarne Winther Kristensen

Published in: Journal of Neuro-Oncology | Issue 1/2016

Abstract

Glioblastoma (GBM) is the most frequent and malignant brain tumor with an overall survival of only 14.6 months. Although these tumors are treated with surgery, radiation and chemotherapy, recurrence is inevitable. A critical population of tumor cells in terms of therapy, the so-called cancer stem cells (CSCs), has been identified in gliomas and many other cancers. These tumor cells have a stem cell-like phenotype and are suggested to be responsible for tumor growth, chemo- and radio-resistance as well as recurrence. However, functional evidence for migrating glioma cells having a stem cell-like phenotype is currently lacking. In the present study, the aim was to characterize the phenotype of migrating tumor cells using a novel migration assay based on serum-free stem cell medium and patient-derived spheroid cultures. The results showed pronounced migration of five different GBM spheroid cultures, but not of the commercial cell line U87MG. An in vitro limiting dilution assay showed preserved but reduced spheroid formation capacity of migrating cells. Orthotopic xenografting in mice showed preserved but reduced tumorigenic capacity. Profiling of mRNAs revealed no significant deregulation of 16 predefined CSC-related genes and the HOX-gene list in migrating cells compared to spheroids. Determination of GBM molecular subtypes revealed that subtypes of spheroids and migrating cells were identical. In conclusion, migrating tumor cells preserve expression of stem cell markers and functional CSC characteristics. Since CSCs are reported to be highly resistant to therapy, these results emphasize that the CSC phenotype should be taken into consideration in future treatment of GBMs.

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Title: Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting
Authors: Sune Munthe
Mia D. Sørensen
Mads Thomassen
Mark Burton
Torben A. Kruse
Justin D. Lathia
Frantz Rom Poulsen
Bjarne Winther Kristensen
Publication date: 01-10-2016
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2016
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2221-y

Keynote webinar | Spotlight on sleep in brain health

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Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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